Identifying drugs for and diagnosis of benign prostatic hyperplasia using gene expression profiles

ABSTRACT

The present invention is based on the elucidation of the global changes in gene expression in prostate tissue isolated from patients exhibiting different clinical states of prostate hyperplasia as compared to normal prostate tissue as well as the identification of individual genes that are differentially expressed in diseased prostate tissue.

RELATED APPLICATIONS

[0001] This application claims priority of U.S. Provisional Application No. 60/223,323, filed Aug. 7, 2000, and U.S. application Ser. No. 09/873,319, filed Jun. 5, 2001, which are herein incorporated by reference in their entirety.

BACKGROUND OF THE INVENTION

[0002] Benign Prostatic Hyperplasia (BPH) is the most common benign tumor in men aged >60 years. It is estimated that one in four men living to the age of 80 will require treatment for this disease. BPH is usually noted clinically after the age of 50, the incidence increasing with age, but as many as two thirds of men between the ages of 40 and 49 demonstrate histological evidence of the disease.

[0003] The anatomic location of the prostate at the bladder neck enveloping the urethra plays an important role in the pathology of BPH, including bladder outlet obstruction. Two prostate components are thought to play a role in bladder outlet obstruction. The first is the relative increased prostate tissue mass. The second component is the prostatic smooth muscle tone.

[0004] The causative factors of BPH in man have been intensively studied. See Ziada et al., Urology, 53: 1-6, 1999. In general, the two most important factors appear to be aging and the presence of functional testes. Although these factors appear to be key to the development of BPH, both appear to be nonspecific.

[0005] Little is known about the molecular changes in prostate cells associated with the development and progression of BPH. It has been demonstrated that the expression levels of a number of individual genes are changed compared to normal prostate cells. These changes in gene expression include decreased expression of Wilm's tumor gene (WT-1) and increased expression of insulin growth factor II (IGF-II) (Dong et al., J. Clin. Endocrin. Metab., 82(7): 2198-220).

[0006] While the changes in the expression levels of a number of individual genes have been identified, the investigation of the global changes in gene expression has not been reported. Accordingly, there exists a need for the investigation of the changes in global gene expression levels as well as the need for the identification of new molecular markers associated with the development and progression of BPH. Furthermore, if intervention is expected to be successful in halting or slowing down BPH, means of accurately assessing the early manifestations of BPH need to be established. One way to accurately assess the early manifestations of BPH is to identify markers which are uniquely associated with disease progression. Likewise, the development of therapeutics to prevent or stop the progression of BPH relies on the identification of genes responsible for BPH growth and function.

SUMMARY OF THE INVENTION

[0007] The present invention is based on the elucidation of the global changes in gene expression in BPH tissue isolated from patients exhibiting different clinical states of prostate hyperplasia as compared to normal prostate tissue as well as the identification of individual genes that are differentially expressed in BPH tissue.

[0008] The invention is also based on the discovery of a means of effectively selecting disease-linked drug targets from gene expression results. The invention includes methods of classifying genes whose expression levels are changed in diseased tissues, during disease induction or during disease progression into specific groups. By using this method it is possible to classify genes whose expression are regulated by the same mechanism into the same group, and it is possible to identify representative marker genes by selecting typical genes from each cluster.

[0009] The invention includes methods of screening for or identifying an agent that modulates the onset or progression of BPH, comprising: preparing a first gene expression profile of BPH cells; exposing the cells to the agent; preparing a second gene expression profile of the agent exposed cells; and comparing the first and second gene expression profiles. In a preferred embodiment of these methods, the gene expression profile comprises the expression levels of one or more or preferably two or more genes in Tables 1-6. In another preferred embodiment of these methods, the cell is a prostate cell from a BPH patient, a cell line in Table 7, or a derivative thereof.

[0010] The invention also includes methods of monitoring a treatment of a patient with BPH, comprising administering a pharmaceutical composition to the patient; preparing a gene expression profile from a prostate cell or tissue sample from the patient; and comparing the patient gene expression profile to a gene expression profile from a normal prostate cell population, a BPH tissue or BPH cells without treatment with the pharmaceutical composition. In preferred embodiments of these methods, the gene expression profile comprises the expression levels of one or more or, preferably two or more genes in Tables 1-6.

[0011] The invention also includes methods of diagnosing benign prostatic hyperplasia (BPH) in a subject comprising the step of detecting the level of expression in a tissue or cell sample from the subject of two or more genes from Tables 1-6 (preferably Tables 3-5, and more preferably Table 5); wherein differential expression of the genes is indicative of BPH progression.

[0012] The invention further includes methods of detecting the onset or progression of benign prostatic hyperplasia (BPH) in a patient comprising the step of detecting the level of expression in a tissue or cell sample of two or more genes from Tables 1-6 (preferably Tables 3-5, and more preferably Table 5); wherein differential expression of the genes is indicative of BPH progression.

[0013] The invention also includes methods of differentiating benign prostatic hyperplasia (BPH) from prostate cancer in a patient comprising the step of detecting the level of expression in a tissue or cell sample of two or more genes from Tables 1-6 (preferably Tables 3-5, and more preferably Table 5); wherein differential expression of the genes is indicative of BPH rather than prostate cancer.

[0014] The invention also includes methods of selecting or identifying cells that can be used for drug screening.

[0015] All of these methods may include the step of detecting the expression levels of at least about 2, 3, 4, 5, 6, 7, 8, 9, 10 or more genes in any of Tables 1-6, or preferably Table 5. In a preferred embodiment, expression of all of the genes or nearly all of the genes in Tables 1-6, or preferably Table 5, may be detected.

[0016] The invention further includes sets of at least two or more probes, wherein each of the probes comprises a sequence that specifically hybridizes to a gene in Tables 1-6 as well as solid supports comprising at least two or more of the probes.

[0017] The invention also includes computer systems comprising or linked to a database containing information identifying the expression level in BPH tissue or cells of a set of genes comprising at least two genes in Tables 1-6, preferably from Table 5; and a user interface to view the information. The database may further comprise sequence information for the genes as well as information identifying the expression level for the set of genes in normal prostate tissue or cells, and prostate cancer tissue. The database may further contain or be linked to descriptive information from an external database, which information correlates said genes to records in the external database.

[0018] The invention further includes methods of using the disclosed computer systems to present information identifying the expression level in a tissue or cell of a set of genes comprising at least one of the genes in Tables 1-6, preferably Table 5, comprising comparing the expression level of at least one gene in Tables 1-6, preferably Table 5, in the tissue or cell to the level of expression of the gene in the database.

[0019] Lastly, the invention includes kits comprising probes or solid supports of the invention. In some embodiments, the kits also contain written materials or software concerning gene expression information for the genes of the invention, preferably in electronic format.

BRIEF DESCRIPTION OF THE DRAWINGS

[0020]FIG. 1. FIG. 1 shows the expression of cellular retinol binding protein RNA in various tissues.

[0021]FIG. 2. FIG. 2 shows the expression of cellular retinol binding protein RNA in various prostate tissues samples. In all of the figures, “Normal”, “-Sym”, “Cancer” and “+Sym” refer to normal prostate, BPH without symptoms, prostate cancer, and BPH with symptoms, respectively.

[0022]FIG. 3. FIG. 3 shows the expression of S100 calcium binding protein RNA in various tissues.

[0023]FIG. 4. FIG. 4 shows the expression of S100 calcium binding protein RNA in various prostate tissue samples.

[0024]FIG. 5. FIG. 5 shows the expression of human prostate-specific membrane antigen (PSMA) RNA in various tissues.

[0025]FIG. 6. FIG. 6 shows the expression of PSMA RNA in various prostate tissue samples.

[0026] FIGS. 7A-7C. FIG. 7A shows a 3-dimensional view of the results of a Preferred Component Analysis (PCA) comparing BPH patients with symptoms (S), asymptomatic BPH patients (O), asymptomatic BPH patients with prostate cancer (C) and normal control subjects (N). FIG. 7B shows the same PCA in a 2-dimensional format plotting component 1 versus components 2+3. The patients are depicted here as: BPH patients with symptoms (BPHWS), asymptomatic BPH patients (BPHNoS), asymptomatic BPH patients with prostate cancer (Cancer) and normal control subjects (Normal). FIG. 7C depicts the same data as FIG. 7B, with the addition of two additional normal (Norm) and three additional BPH patients with symptoms (BPH).

DETAILED DESCRIPTION

[0027] Many biological functions are accomplished by altering the expression of various genes through transcriptional (e.g. through control of initiation, provision of RNA precursors, RNA processing, etc.) and/or translational control. For example, fundamental biological processes such as cell cycle, cell differentiation and cell death, are often characterized by the variations in the expression levels of groups of genes.

[0028] Changes in gene expression also are associated with pathogenesis. For example, the lack of sufficient expression of functional tumor suppressor genes and/or the over expression of oncogene/protooncogenes could lead to tumorgenesis or hyperplastic growth of cells (Marshall, Cell, 64: 313-326 (1991); Weinberg, Science, 254:1138-1146 (1991)). Thus, changes in the expression levels of particular genes (e.g. oncogenes or tumor suppressors) serve as signposts for the presence and progression of various diseases.

[0029] Monitoring changes in gene expression may also provide certain advantages during drug screening development. Often drugs are screened for the ability to interact with a major target without regard to other effects the drugs have on cells. Often such other effects cause toxicity in the whole animal, which prevent the development and use of the potential drug.

[0030] The present inventors have examined tissue from normal prostate, BPH and BPH prostate tissue immediately adjacent to malignant prostate tissue to identify the global changes in gene expression in BPH. These changes in gene expression, also referred to as expression profiles, provide useful markers for diagnostic uses as well as markers that can be used to monitor disease states, disease progression, toxicity, drug efficacy and drug metabolism.

[0031] Assay Formats

[0032] The genes identified as being differentially expressed in BPH tissue or BPH cells (Tables 1-6) may be used in a variety of nucleic acid detection assays to detect or quantititate the expression level of a gene or multiple genes in a given sample. For example, traditional Northern blotting, nuclease protection, RT-PCR and differential display methods may be used for detecting gene expression levels. Those methods are useful for some embodiments of the invention, particularly when smaller numbers of genes are assayed. For instance, when fewer than 50 genes are assayed, RT-PCR techniques can be used to prepare high-throughput assays. However, methods and assays of the invention are most efficiently designed with hybridization-based methods for detecting the expression of a large number of genes.

[0033] Any hybridization assay format may be used, including solution-based and solid support-based assay formats. Solid supports containing oligonucleotide probes for differentially expressed genes of the invention can be filters, polyvinyl chloride dishes, silicon or glass based beads or chips, etc. Such supports and hybridization methods are widely available, for example, those disclosed by Beattie (WO 95/11755). Any solid surface to which oligonucleotides can be bound, either directly or indirectly, either covalently or non-covalently, can be used.

[0034] A preferred solid support is a high density array or DNA chip. These contain a particular oligonucleotide probe in a predetermined location on the array. Each predetermined location may contain more than one molecule of the probe, but each molecule within the predetermined location has an identical sequence. Such predetermined locations are termed features. There may be, for example, from 2, 10, 100, 1000 to 10,000, 100,000 or 400,000 of such features on a single solid support. The solid support, or the area within which the probes are attached may be on the order of about a square centimeter.

[0035] Oligonucleotide probe arrays for expression monitoring can be made and used according to any technique known in the art (see for example, Lockhart et al., Nat. Biotechnol. (1996) 14, 1675-1680; McGall et al., Proc. Nat. Acad. Sci. USA (1996) 93, 13555-13460). Such probe arrays may contain at least two or more oligonucleotides that are complementary to or hybridize to two or more of the genes described in Tables 1-6. For instance, such arrays may contain oligonucleotides that are complementary or hybridize to at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 50, 70 or more of the genes described herein.

[0036] The genes which are assayed according to the present invention are typically in the form of mRNA or reverse transcribed mRNA. The genes may be cloned or not. The genes may be amplified or not. The cloning itself does not appear to bias the representation of genes within a population. However, it may be preferable to use polyA+ RNA as a source, as it can be used with less processing steps.

[0037] The sequences and related information of the genes described herein are available in the public databases. Tables 1-6 provide the Accession numbers and name for each of the sequences. Each Accession Number corresponds to a sequence in the attached sequence listing. The sequences and related information of the genes listed in the Tables according to their GenBank identifiers are expressly incorporated herein as of the filing date of this application, as are sequences in the databases related to those herein described, such as fragments, variant sequences, etc. (see: www.ncbi.nlm.gov).

[0038] Probes based on the sequences of the genes described above may be prepared by any commonly available method. Oligonucleotide probes for interrogating the tissue or cell sample are preferably of sufficient length to specifically hybridize only to appropriate, complementary genes or transcripts. Typically the oligonucleotide probes will be at least 10, 12, 14, 16, 18, 20 or 25 nucleotides in length. In some cases longer probes of at least 30, 40, or 50 nucleotides will be desirable.

[0039] As used herein, oligonueleotide sequences that are complementary to one or more of the genes described in Tables 1-6 refer to oligonucleotides that are capable of hybridizing under stringent conditions to at least part of the nucleotide sequence of said genes. Such hybridizable oligonucleotides will typically exhibit at least about 75% sequence identity at the nucleotide level to said genes, preferably about 80% or 85% sequence identity or more preferably about 90% or 95% or more sequence identity to said genes.

[0040] “Bind(s) substantially” refers to complementary hybridization between a probe nucleic acid and a target nucleic acid and embraces minor mismatches that can be accommodated by reducing the stringency of the hybridization media to achieve the desired detection of the target polynucleotide sequence.

[0041] The terms “background” or “background signal intensity” refer to hybridization signals resulting from non-specific binding, or other interactions, between the labeled target nucleic acids and components of the oligonucleotide array (e.g., the oligonucleotide probes, control probes, the array substrate, etc.). Background signals may also be produced by intrinsic fluorescence of the array components themselves. A single background signal can be calculated for the entire array, or a different background signal may be calculated for each target nucleic acid. In a preferred embodiment, background is calculated as the average hybridization signal intensity for the lowest 5% to 10% of the probes in the array, or, where a different background signal is calculated for each target gene, for the lowest 5% to 10% of the probes for each gene. Of course, one of skill in the art will appreciate that where the probes to a particular gene hybridize well and thus appear to be specifically binding to a target sequence, they should not be used in a background signal calculation. Alternatively, background may be calculated as the average hybridization signal intensity produced by hybridization to probes that are not complementary to any sequence found in the sample (e.g. probes directed to nucleic acids of the opposite sense or to genes not found in the sample such as bacterial genes where the sample is mammalian nucleic acids). Background can also be calculated as the average signal intensity produced by regions of the array that lack probes.

[0042] The phrase “hybridizing specifically to” refers to the binding, duplexing, or hybridizing of a molecule substantially to or only to a particular nucleotide sequence or sequences under stringent conditions when that sequence is present in a complex mixture (e.g., total cellular DNA or RNA).

[0043] Assays and methods of the invention may utilize available formats to simultaneously screen at least about 100, preferably about 1000, more preferably about 10,000 and most preferably about 1,000,000 different nucleic acid hybridizations.

[0044] As used herein a “probe” is defined as a nucleic acid molecule, capable of binding to a target nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing, usually through hydrogen bond formation. As used herein, a probe may include natural (i.e., A, G, U, C, or T) or modified bases (7-deazaguanosine, inosine, etc.). In addition, the bases in probes may be joined by a linkage other than a phosphodiester bond, so long as it does not interfere with hybridization. Thus, probes may be peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages.

[0045] The term “stringent conditions” refers to conditions under which a probe will hybridize to its target subsequence, but with only insubstantial hybridization to other sequences or to other sequences such that the difference may be identified. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH.

[0046] Typically, stringent conditions will be those in which the salt concentration is at least about 0.01 to 1.0 M Na ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30° C. for short probes (e.g., 10 to 50 nucleotide). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide.

[0047] The “percentage of sequence identity” or “sequence identity” is determined by comparing two optimally aligned sequences or subsequences over a comparison window or span, wherein the portion of the polynucleotide sequence in the comparison window may optionally comprise additions or deletions (i.e., gaps) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences.

[0048] The percentage is calculated by determining the number of positions at which the identical submit (e.g. nucleic acid base or amino acid residue) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence identity. Percentage sequence identity when calculated using the programs GAP or BESTFIT (see below) is calculated using default gap weights.

[0049] Probe Design

[0050] One of skill in the art will appreciate that an enormous number of array designs are suitable for the practice of this invention. The high density array will typically include a number of probes that specifically hybridize to the sequences of interest. See WO 99/32660 for methods of producing probes for a given gene or genes. In addition, in a preferred embodiment, the array will include one or more control probes.

[0051] High density array chips of the invention include “test probes.” Test probes could be oligonucleotides that range from about 5 to about 500 or 5 to about 45 nucleotides, more preferably from about 10 to about 40 nucleotides and most preferably from about 15 to about 40 nucleotides in length. In other particularly preferred embodiments the probes are 20 or 25 nucleotides in length. In another preferred embodiment, test probes are double or single strand DNA sequences. DNA sequences are isolated or cloned from natural sources or amplified from natural sources using native nucleic acid as templates. These probes have sequences complementary to particular subsequences of the genes whose expression they are designed to detect. Thus, the test probes are capable of specifically hybridizing to the target nucleic acid they are to detect (the genes of Tables 1-6).

[0052] The term “perfect match probe” refers to a probe that has a sequence that is perfectly complementary to a particular target sequence. The probe is typically perfectly complementary to a portion (subsequence) of the target sequence. The perfect match (PM) probe can be a “test probe”, a “normalization control” probe, an expression level control probe and the like. A perfect match control or perfect match probe is, however, distinguished from a “mismatch control” or “mismatch probe.”

[0053] In addition to test probes that bind the target nucleic acid(s) of interest, the high density array can contain a number of control probes. The control probes fall into three categories referred to herein as 1) normalization controls; 2) expression level controls; and 3) mismatch controls.

[0054] Normalization controls are oligonucleotide or other nucleic acid probes that are complementary to labeled reference oligonucleotides or other nucleic acid sequences that are added to the nucleic acid sample to be screened. The signals obtained from the normalization controls after hybridization provide a control for variations in hybridization conditions, label intensity, “reading” efficiency and other factors that may cause the signal of a perfect hybridization to vary between arrays. In a preferred embodiment, signals (e.g., fluorescence intensity) read from all other probes in the array are divided by the signal (e.g., fluorescence intensity) from the control probes thereby normalizing the measurements.

[0055] Virtually any probe may serve as a normalization control. However, it is recognized that hybridization efficiency varies with base composition and probe length. Preferred normalization probes are selected to reflect the average length of the other probes present in the array, however, they can be selected to cover a range of lengths. The normalization control(s) can also be selected to reflect the (average) base composition of the other probes in the array, however in a preferred embodiment, only one or a few probes are used and they are selected such that they hybridize well (i.e., no secondary structure) and do not match any target-specific probes.

[0056] Expression level controls are probes that hybridize specifically with constitutively expressed genes in the biological sample. Virtually any constitutively expressed gene provides a suitable target for expression level controls. Typically expression level control probes have sequences complementary to subsequences of constitutively expressed “housekeeping genes” including, but not limited to an actin gene, the transferrin receptor gene, the GAPDH gene, and the like.

[0057] Mismatch controls or mismatch probes may also be provided for the probes to the target genes, for expression level controls or for normalization controls. Mismatch controls are oligonucleotide probes or other nucleic acid probes identical to their corresponding test or control probes except for the presence of one or more mismatched bases. A mismatched base is a base selected so that it is not complementary to the corresponding base in the target sequence to which the probe would otherwise specifically hybridize. One or more mismatches are selected such that under appropriate hybridization conditions (e.g., stringent conditions) the test or control probe would be expected to hybridize with its target sequence, but the mismatch probe would not hybridize (or would hybridize to a significantly lesser extent). Preferred mismatch probes contain a central mismatch. Thus, for example, where a probe is a 20 mer, a corresponding mismatch probe will have the identical sequence except for a single base mismatch (e.g., substituting a G, a C or a T for an A) at any of positions 6 through 14 (the central mismatch).

[0058] Mismatch probes thus provide a control for non-specific binding or cross hybridization to a nucleic acid in the sample other than the target to which the probe is directed. Mismatch probes also indicate whether a hybridization is specific or not. For example, if the target is present the perfect match probes should be consistently brighter than the mismatch probes. In addition, if all central mismatches are present, the mismatch probes can be used to detect a mutation. The difference in intensity between the perfect match and the mismatch probe provides a good measure of the concentration of the hybridized material.

[0059] Nucleic Acid Samples

[0060] As is apparent to one of ordinary skill in the art, nucleic acid samples used in the methods and assays of the invention may be prepared by any available method or process. Methods of isolating total mRNA are well known to those of skill in the art. For example, methods of isolation and purification of nucleic acids are described in detail in Chapter 3 of Laboratory Techniques in Biochemistry and Molecular Biology: Hybridization With Nucleic Acid Probes, Part I Theory and Nucleic Acid Preparation, P. Tijssen, Ed., Elsevier, N.Y. (1993). Such samples include RNA samples, but also include cDNA synthesized from a mRNA sample isolated from a cell or tissue of interest. Such samples also include DNA amplified from the cDNA, and RNA transcribed from the amplified DNA. One of skill in the art would appreciate that it is desirable to inhibit or destroy RNase present in homogenates before homogenates can be used.

[0061] Biological samples may be of any biological tissue or fluid or cells from any organism as well as cells raised in vitro, such as cell lines and tissue culture cells. Biological samples may also include sections of tissues, such as frozen sections or formalin fixed sections taken for histological purposes. Frequently, the sample will be a “clinical sample” which is a sample derived from a patient. Typical clinical samples include, but are not limited to prostate tissue, urine, sputum, blood, blood-cells (e.g., white cells or peripheral blood leukocytes (PBL), tissue or fine needle biopsy samples, peritoneal fluid, and pleural fluid, or cells therefrom.

[0062] Forming High Density Arrays.

[0063] Methods of forming high density arrays of oligonucleotides with a minimal number of synthetic steps are known. The oligonucleotide analogue array can be synthesized on a solid substrate by a variety of methods, including, but not limited to, light-directed chemical coupling, and mechanically directed coupling. See Pirrung et al., U.S. Pat. No. 5,143,854.

[0064] In brief, the light-directed combinatorial synthesis of oligonucleotide arrays on a glass surface proceeds using automated phosphoramidite chemistry and chip masking techniques. In one specific implementation, a glass surface is derivatized with a silane reagent containing a functional group, e.g., a hydroxyl or amine group blocked by a photolabile protecting group. Photolysis through a photolithogaphic mask is used selectively to expose functional groups which are then ready to react with incoming 5′ photoprotected nucleoside phosphoramidites. The phosphoramidites react only with those sites which are illuminated (and thus exposed by removal of the photolabile blocking group). Thus, the phosphoramidites only add to those areas selectively exposed from the preceding step. These steps are repeated until the desired array of sequences have been synthesized on the solid surface. Combinatorial synthesis of different oligonucleotide analogues at different locations on the array is determined by the pattern of illumination during synthesis and the order of addition of coupling reagents.

[0065] In addition to the foregoing, additional methods which can be used to generate an array of oligonucleotides on a single substrate are described in WO 93/09668. High density nucleic acid arrays can also be fabricated by depositing premade or natural nucleic acids in predetermined positions. Synthesized or natural nucleic acids are deposited on specific locations of a substrate by light directed targeting and oligonucleotide directed targeting. Another embodiment uses a dispenser that moves from region to region to deposit nucleic acids in specific spots.

[0066] Hybridization

[0067] Nucleic acid hybridization simply involves contacting a probe and target nucleic acid under conditions where the probe and its complementary target can form stable hybrid duplexes through complementary base pairing. See WO 99/32660. The nucleic acids that do not form hybrid duplexes are then washed away leaving the hybridized nucleic acids to be detected, typically through detection of an attached detectable label. It is generally recognized that nucleic acids are denatured by increasing the temperature or decreasing the salt concentration of the buffer containing the nucleic acids. Under low stringency conditions (e.g., low temperature and/or high salt) hybrid duplexes (e.g., DNA:DNA, RNA:RNA, or RNA:DNA) will form even where the annealed sequences are not perfectly complementary.

[0068] Thus specificity of hybridization is reduced at lower stringency. Conversely, at higher stringency (e.g., higher temperature or lower salt) successful hybridization tolerates fewer mismatches. One of skill in the art will appreciate that hybridization conditions may be selected to provide any degree of stringency. In a preferred embodiment, hybridization is performed at low stringency in this case in 6× SSPE-T at 37° C. (0.005% Triton X-100) to ensure hybridization and then subsequent washes are performed at higher stringency (e.g., I× SSPE-T at 37° C.) to eliminate mismatched hybrid duplexes. Successive washes may be performed at increasingly higher stringency (e.g., down to as low as 0.25× SSPET at 37° C. to 50° C.) until a desired level of hybridization specificity is obtained. Stringency can also be increased by addition of agents such as formamide. Hybridization specificity may be evaluated by comparison of hybridization to the test probes with hybridization to the various controls that can be present (e.g., expression level control, normalization control, mismatch controls, etc.).

[0069] In general, there is a tradeoff between hybridization specificity (stringency) and signal intensity. Thus, in a preferred embodiment, the wash is performed at the highest stringency that produces consistent results and that provides a signal intensity greater than approximately 10% of the background intensity. Thus, in a preferred embodiment, the hybridized array may be washed at successively higher stringency solutions and read between each wash. Analysis of the data sets thus produced will reveal a wash stringency above which the hybridization pattern is not appreciably altered and which provides adequate signal for the particular oligonucleotide probes of interest.

[0070] Signal Detection

[0071] The hybridized nucleic acids are typically detected by detecting one or more labels attached to the sample nucleic acids. The labels may be incorporated by any of a number of means well known to those of skill in the art. See WO 99/32660.

[0072] Databases

[0073] The present invention includes relational databases containing sequence information, for instance for the genes of Tables 1-6, as well as gene expression information in various prostate tissue samples. Databases may also contain information associated with a given sequence or tissue sample such as descriptive information about the gene associated with the sequence information, metabolic pathway information for the gene or descriptive information concerning the clinical status of the tissue sample, or the patient from which the sample was derived. Such information for the patient may include, but is not limited to sex, age, disease status, general health information, surgical or treatment status, PSA levels, as well as information concerning the patient's clinical symptoms. The database may be designed to include different parts, for instance a sequence database and a gene expression database. Methods for the configuration and construction of such databases are widely available, for instance, see U.S. Pat. No. 5,953,727, which is herein incorporated by reference in its entirety.

[0074] The databases of the invention may be linked to an outside or external database. In a preferred embodiment, as described in Tables 1-6, the external database is GenBank and the associated databases maintained by the National Center for Biotechnology Information (NCBI).

[0075] Any appropriate computer platform may be used to perform the necessary comparisons between sequence information, gene expression information and any other information in the database or provided as an input. For example, a large number of computer workstations are available from a variety of manufacturers, such has those available from Silicon Graphics. Client/server environments, database servers and networks are also widely available and appropriate platforms for the databases of the invention.

[0076] The databases of the invention may be used to produce, among other things, electronic Northerns that allow the user to determine the cell type or tissue in which a given gene is expressed and to allow determination of the abundance or expression level of a given gene in a particular tissue or cell.

[0077] The databases of the invention may also be used to present information identifying the expression level in a tissue or cell of a set of genes comprising at least two of the genes in Tables 1-6, comprising the step of comparing the expression level of at least one gene in Tables 1-6 found or detected in the tissue to the level of expression of the gene in the database. Such methods may be used to predict the hyperplastic state of a given tissue by comparing the level of expression of a gene or genes in Tables 1-6 from a sample to the expression levels found in normal prostate cells, BPH cells or tissue and/or malignant or cancerous prostate tissue. Such methods may also be used in the drug or agent screening assays as described below.

[0078] Selection of BPH-Associated Genes

[0079] BPH associated genes may be identified or selected by any available method, including subtractive hybridization protocols, differential display protocols and high-throughput hybridization formats, including oligonucleotide and cDNA microarray technologies.

[0080] Unprocessed or raw expression levels may be normalized, standardized and/or analyzed by any available computational method, including the expression level normalization, analysis and clustering methods herein described. The normalization method as described in Example 4 may be combined with any further analysis method, including any clustering methods available in the art.

[0081] Diagnostic Uses for the BPH Markers

[0082] As described above, the genes and gene expression information provided in Tables 1-1s 6 may be used as diagnostic markers for the prediction or identification of the hyperplastic state of a prostate or other tissue. For instance, a prostate tissue or other patient sample may be assayed by any of the methods described above, and the expression levels from a gene or genes from Tables 1-6 may be compared to the expression levels found in normal prostate tissue, BPH tissue or BPH tissue from a patient with metastatic or nonmetastatic prostate cancer. In some instances, patient PBLs may be used as the patient sample. The comparison of expression data, as well as available sequence or other information may be done by researcher or diagnostician or may be done with the aid of a computer and databases as described above.

[0083] Use of the BPH Markers for Monitoring Disease Progression

[0084] As described above, the genes and gene expression information provided in Tables 1-6 may also be used as markers for the monitoring of disease progression, such as the development of BPH. For instance, a prostate tissue or other patient sample may be assayed by any of the methods described above, and the expression levels from a gene or genes from Tables 1-6 may be compared to the expression levels found in normal prostate tissue, BPH tissue or BPH tissue from a patient with metastatic or nonmetastatic prostate cancer. The comparison of the expression data, as well as available sequence or other information may be done by researcher or diagnostician or may be done with the aid of a computer and databases as described above.

[0085] The BPH markers of the invention may also be used to track or predict the progress or efficacy of a treatment regime in a patient. For instance, a patient's progress or response to a given drug may be monitored by creating a gene expression profile from a tissue or cell sample after treatment or administration of the drug. The gene expression profile may then be compared to a gene expression profile prepared from normal cells or tissue, for instance, normal prostate tissue. The gene expression profile may also be compared to a gene expression profile prepared from BPH or malignant prostate cells, or from tissue or cells from the same patient before treatment. The gene expression profile may be made from at least one gene, preferably more than one gene, and most preferably all or nearly all of the genes in Tables 1-6.

[0086] Use of the BPH Markers for Drug Screening

[0087] According to the present invention, the genes identified in Tables 1-6 can be used as markers to screen for potential therapeutic agents or compounds to treat BPH or prostate cancer. A candidate drug or agent can be screened for the ability to stimulate the transcription or expression of a given marker or to down-regulate or counteract the transcription or expression of a marker or markers. Compounds that modulate the expression level of single gene and also compounds that modulate the expression level of multiple genes from levels associated with a specific disease state to a normal state can be screened by using the markers and profiles identified herein.

[0088] According to the present invention, one can also compare the specificity of drug's effects by looking at the number of markers which are differentially expressed after drug exposure and comparing them. More specific drugs will have less transcriptional targets. Similar sets of markers identified for two drugs may indicate a similarity of effects.

[0089] Assays to monitor the expression of a marker or markers as defined in Tables 1-6 may utilize any available means of monitoring for changes in the expression level of the nucleic acids of the invention. As used herein, an agent is said to modulate the expression of a nucleic acid of the invention if it is capable of up- or down-regulating expression of the nucleic acid in a cell.

[0090] In one assay format, gene chips containing probes to at least 2 genes from Tables 1-6 may be used to directly monitor or detect changes in gene expression in the treated or exposed cell as described in more detail above. In another format, the changes of mRNA expression level can be detected using QuantiGene technology (Warrior et. al. (2000) J. Biomolecular Screening, 5, 343-351). Specific probes used for QuantiGene can be designed and synthesized to one or more genes from Tables 1-6. Cells treated with compounds are lysed by lysis buffer. The amount of target mRNA can be detected as a luminescence intensity using target specific probes.

[0091] In another format, cell lines that contain reporter gene fusions between the open reading frame and/or 5′/3′ regulatory regions of a gene in Tables 1-6 and any assayable fusion partner may be prepared. Numerous assayable fusion partners are known and readily available including the firefly luciferase gene and the gene encoding chloramphenicol acetyltransferase (Alam et al. (1990) Anal. Biochem. 188:245-254). Cell lines containing the reporter gene fusions are then exposed to the agent to be tested under appropriate conditions and time. Differential expression of the reporter gene between samples exposed to the agent and control samples identifies agents which modulate the expression of the nucleic acid.

[0092] Additional assay formats may be used to monitor the ability of the agent to modulate the expression of a gene identified in Tables 1-6. For instance, as described above, mRNA expression may be monitored directly by hybridization of probes to the nucleic acids of the invention. Cell lines are exposed to the agent to be tested under appropriate conditions and time and total RNA or mRNA is isolated by standard procedures such those disclosed in Sambrook et al. (Molecular Cloning: A Laboratory Manual, 2nd Ed. Cold Spring Harbor Laboratory Press, 1989).

[0093] In another assay format, cells or cell lines are first identified which express the gene products of the invention physiologically (see below). Cell and/or cell lines so identified would be expected to comprise the necessary cellular machinery such that the fidelity of modulation of the transcriptional apparatus is maintained with regard to exogenous contact of agent with appropriate surface transduction mechanisms and/or the cytosolic cascades. Such cell lines may be, but are not required to be, prostate derived. Further, such cells or cell lines may be transduced or transfected with an expression vehicle (e.g., a plasmid or viral vector) construct comprising an operable non-translated 5′-promoter containing end of the structural gene encoding the instant gene products fused to one or more antigenic fragments, which are peculiar to the instant gene products, wherein said fragments are under the transcriptional control of said promoter and are expressed as polypeptides whose molecular weight can be distinguished from the naturally occurring polypeptides or may further comprise an immunologically distinct tag or some other detectable marker or tag. Such a process is well known in the art (see Maniatis).

[0094] Cells or cell lines transduced or transfected as outlined above are then contacted with agents under appropriate conditions; for example, the agent comprises a pharmaceutically acceptable excipient and is contacted with cells comprised in an aqueous physiological buffer such as phosphate buffered saline (PBS) at physiological pH, Eagles balanced salt solution (BSS) at physiological pH, PBS or BSS comprising serum or conditioned media comprising PBS or BSS and/or serum incubated at 37° C. Said conditions may be modulated as deemed necessary by one of skill in the art. Subsequent to contacting the cells with the agent, said cells are disrupted and the polypeptides of the lysate are fractionated such that a polypeptide fraction is pooled and contacted with an antibody to be further processed by immunological assay (e.g., ELISA, immunoprecipitation or Western blot). The pool of proteins isolated from the “agent-contacted” sample is then compared with a control sample where only the excipient is contacted with the cells and an increase or decrease in the immunologically generated signal from the “agent-contacted” sample compared to the control is used to distinguish the effectiveness of the agent.

[0095] Another embodiment of the present invention provides methods for identifying agents that modulate at least one activity of a protein(s) encoded by the genes in Tables 1-6. Such methods or assays may utilize any means of monitoring or detecting the desired activity.

[0096] In one format, the relative amounts of a protein of the invention between a cell population that has been exposed to the agent to be tested compared to an un-exposed control cell population may be assayed. In this format, probes such as specific antibodies are used to monitor the differential expression of the protein in the different cell populations. Cell lines or populations are exposed to the agent to be tested under appropriate conditions and time. Cellular lysates may be prepared from the exposed cell line or population and a control, unexposed cell line or population. The cellular lysates are then analyzed with the probe, such as a specific antibody.

[0097] Agents that are assayed in the above methods can be randomly selected or rationally selected or designed. As used herein, an agent is said to be randomly selected when the agent is chosen randomly without considering the specific sequences involved in the association of the a protein of the invention alone or with its associated substrates, binding partners, etc. An example of randomly selected agents is the use a chemical library or a peptide combinatorial library, or a growth broth of an organism.

[0098] As used herein, an agent is said to be rationally selected or designed when the agent is chosen on a nonrandom basis which takes into account the sequence of the target site and/or its conformation in connection with the agent's action. Agents can be rationally selected or at rationally designed by utilizing the peptide sequences that make up these sites. For example, a rationally selected peptide agent can be a peptide whose amino acid sequence is identical to or a derivative of any functional consensus site.

[0099] The agents of the present invention can be, as examples, peptides, small molecules, vitamin derivatives, as well as carbohydrates. Dominant negative proteins, DNAs encoding these proteins, antibodies to these proteins, peptide fragments of these proteins or mimics of these proteins may be introduced into cells to affect function. “Mimic” used herein refers to the modification of a region or several regions of a peptide molecule to provide a structure chemically different from the parent peptide but topographically and functionally similar to the parent peptide (see Grant G A. in: Meyers (ed.) Molecular Biology and Biotechnology (New York, VCH Publishers, 1995), pp. 659-664). A skilled artisan can readily recognize that there is no limit as to the structural nature of the agents of the present invention.

[0100] Cells Used for Multi Gene Screening

[0101] Many kinds of cells such as primary cells and cell lines can be used for the drug screening methods of the invention. Cells or cell lines derived from prostatic tissues are preferred because the innate gene expression mechanisms of these cells often resemble those of prostatic tissues. Cells used for drug screening can be selected by assaying for the expression of one or more of the marker genes listed in Tables 1-6. The cells which differentially express one or more, or preferably nearly all of the marker genes listed in Tables 1-6 are preferred cells or cell lines for the methods of the invention (see Table 7).

[0102] Kits

[0103] The invention further includes kits combining, in different combinations, high-density oligonucleotide arrays, reagents for use with the arrays, signal detection and array-processing instruments, gene expression databases and analysis and database management software described above. The kits may be used, for example, to diagnose the disease state of a tissue or cell sample, to monitor the progression of prostate disease states, to identify genes that show promise as new drug targets and to screen known and newly designed drugs as discussed above.

[0104] The databases packaged with the kits are a compilation of expression patterns from human and laboratory animal genes and gene fragments (corresponding to the genes of Tables 1-6). In particular, the database software and packaged information include the expression results of Tables 1-6 that can be used in the assays and methods as herein described. In another format, database access is provided to the purchaser or user through an electronic means, e.g., via the Internet or by direct dial-in access.

[0105] The kits may used in the pharmaceutical industry, where the need for early drug testing is strong due to the high costs associated with drug development, but where bioinformatics, in particular gene expression informatics, is still lacking. These kits will reduce the costs, time and risks associated with traditional new drug screening using cell cultures and laboratory animals. The results of large-scale drug screening of pre-grouped patient populations, pharmacogenomics testing, can also be applied to select drugs with greater efficacy and fewer side-effects. The kits may also be used by smaller biotechnology companies and research institutes who do not have the facilities for performing such large-scale testing themselves.

[0106] Databases and software designed for use with use with microarrays is discussed in Balaban et al., U.S. Pat. No. 6,229,911, a computer-implemented method for managing information, stored as indexed tables, collected from small or large numbers of microarrays, and U.S. Pat. No. 6,185,561, a computer-based method with data mining capability for collecting gene expression level data, adding additional attributes and reformatting the data to produce answers to various queries. Chee et al., U.S. Pat. No. 5,974,164, disclose a software-based method for identifying mutations in a nucleic acid sequence based on differences in probe fluorescence intensities between wild type and mutant sequences that hybridize to reference sequences.

[0107] Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the genes, chips, etc. of the present invention and practice the claimed methods. The following working examples therefore, specifically point out the preferred embodiments of the present invention, and are not to be construed as limiting in any way the remainder of the disclosure.

EXAMPLES Example 1 Gene Chip Expression Analysis

[0108] Human tissue was obtained from the transitional zone of the prostate (the junction between the ejaculatory duct and the prostatic urethra) in biopsy samples from normal individuals and from patients with BPH or prostate cancer. BPH was defined histologically in all samples. Normal tissue and asymptomatic BPH samples came from individuals who died of trauma and did not report symptoms. Because BPH is a disease associated with aging, two groups of normal individuals were identified, group 1, ages 20 or under, and group 2, ages 30-50. Patients having BPH with symptoms were defined as those with a need for frequent urination. In these patients, a radical prostatectomy had been performed. Prostate cancer patients provided age-matched tissue samples for symptomatic BPH patients, but were without symptoms and without cancer in the transitional zone under histological examination.

[0109] Microarray sample preparation was conducted with minor modifications, following the protocols set forth in the Affymetrix GeneChip Expression Analysis Manual. Frozen tissue was ground to a powder using a Spex Certiprep 6800 Freezer Mill. Total RNA was extracted with Trizol (GibcoBRL) utilizing the manufacturer's protocol. The total RNA yield for each sample was 200-500 μg per 300 mg tissue weight. mRNA was isolated using the Oligotex mRNA Midi kit (Qiagen) followed by ethanol precipitation. Double stranded cDNA was generated from mRNA using the SuperScript Choice system (GibcoBRL). First strand cDNA synthesis was primed with a T7-(dT24) oligonucleotide. The cDNA was phenol-chloroform extracted and ethanol precipitated to a final concentration of 1 μg/ml. From 2 μg of cDNA, cRNA was synthesized using Ambion's T7 MegaScript in vitro Transcription Kit.

[0110] To biotin label the cRNA, nucleotides Bio-11-CTP and Bio-16-UTP (Enzo Diagnostics) were added to the reaction. Following a 37° C. incubation for six hours, impurities were removed from the labeled cRNA following the RNeasy Mini kit protocol (Qiagen). cRNA was fragmented (fragmentation buffer consisting of 200 mM Tris-acetate, pH 8.1, 500 mM KOAc, 150 mM MgOAc) for thirty-five minutes at 94° C. Following the Affymetrix protocol, 55 μg of fragmented cRNA was hybridized on the Affymetrix Human 42K array set for twenty-four hours at 60 mpm in a 45° C. hybridization oven. The chips were washed and stained with Streptavidin Phycoerythrin (SAPE) (Molecular Probes) in Affymetrix fluidics stations. To amplify staining, SAPE solution was added twice with an anti-streptavidin biotinylated antibody (Vector Laboratories) staining step in between. Hybridization to the probe arrays was detected by fluorometric scanning (Hewlett Packard Gene Array Scanner). Data was analyzed using Affymetrix GeneChip version 3.0 and Expression Data Mining Tool (EDMT) software (version 1.0).

[0111] Differential expression of genes between the BPH and normal prostate samples were determined using the Affymetrix GeneChip human gene chip set by the following criteria: 1) For each gene, Affymetrix GeneChip average difference values were determined by standard Affymetrix EDMT software algorithms, which also made “Absent” (=not specifically detected as gene expression), “Present” (=detected) or “Marginal” (=not clearly Absent or Present) calls for each GeneChip element; 2) all AveDiff values which were less than +20 (positive 20) were raised to a floor of +20 so that fold change calculations could be made where values were not already greater than or equal to +20; 3) median levels of expression were compared between the normal control group and the BPH with symptoms disease group to obtain greater than or equal 2-fold up/down values; 4) The median value for the higher expressing group needed to be greater or equal to 200 average difference units in order to be considered for statistical significance; 5) Genes passing the criteria of #1-4 were analyzed for statistical significance using a two-tailed T test and deemed statistically significant if p<0.05. Tables 1 and 2 list the genes and their levels of differential expression (compared to normal samples) in BPH tissue from patients with symptoms of BPH and in BPH tissue immediately adjacent to malignant prostate tissue isolated from male patients.

Example 2 Expression Profile Analysis

[0112] Gene expression profiles between normal sample and BPH patient samples were determined by using the following samples: 10 normal; 7 BPH without symptoms; 8 BPH with cancer; and 8 BPH with symptoms. Gene expression profiles were prepared using the 42K Affymetrix Gene Chip set. The methods used were the same as described in Example 1 with the exception of the criteria to select the marker genes.

[0113] The criteria used in this study were as follows; 1) For each gene, Affymetrix GeneChip average difference values were determined by standard Affymetrix EDMT software algorithms, which also made “Absent” (=not specifically detected as gene expression), “Present” (=detected) or “Marginal” (=not clearly Absent or Present) calls for each GeneChip element; 2) all AveDiff values which were less than +20 (positive 20) were raised to a floor of +20 so that fold change calculations could be made where values were not already greater than or equal to +20; 3) mean levels of expression were compared between the normal control group and the BPH with symptoms disease group; 4) genes were arranged by the fold change starting with the largest one (Fold change calculation was determined by using logarithmic values in Example 2); and 5) the top 200 up-regulated genes and bottom 200 down-regulated genes were selected. The genes identified in this study are listed in Tables 3 (normal vs. BPH with symptoms, up regulated) and 4 (normal vs. BPH with symptoms, down regulated, values are negative fold-change from normal).

Example 3 Selection of Cell Lines Used for Multi Gene Screening

[0114] A number of cultured cell lines were tested to determine the similarity in gene expression profiles to BPH tissue. Cells were cultured in 6-well plates using the appropriate medium for each cell line. After reaching 90% confluency, cells were lysed with Trizol (GiboBRL) and total RNA was extracted. mRNA was then isolated, cDNA and cRNA was synthesized, and gene expression levels were determined by the Affymetrix Human 42K Gene Chip set as described in more detail above.

[0115] The gene expression profiles were compared with those of prostatic tissue samples. A panel of 61 genes whose expression levels were up-regulated in BPH with symptoms compared with normal samples and with small variation among samples (within BPH samples and within normal samples) were assayed. The group of genes whose signal intensity was more than 100 in each cell line is summarized in Table 1. A panel of 43 genes whose expression levels were down-regulated in BPH patient with small variation among samples was also assayed. The group of genes whose signal intensity in Affymetrix Gene Chip was “Present call” is also included in Table 1. Similarly, genes whose expression level is up- or down-regulated in patients with BPH and cancer, compared to normal controls, are listed in Table 2.

[0116] Forty-eight to 58% of genes applied for this analysis were expressed in the cell lines of Table 7. These results indicate that cell lines, BRF-55T (Biological Research Faculty & Facility Inc.), PZ-HPV7 (ATCC; CRL-2221), BPH-1 (S.W. Hayward et al., In Vitro Cell Dev. Biol. 31A, 14-24, 1995) and LNCaP (ATCC; CRL-1740) can be used as a BPH—like cell population to screen for compounds which are capable of modulating gene expression profiles from the disease state to a normal state using the genes of Tables 1-6. In particular, BRF-55T is a useful cell line for screening in the assays of the invention, because 58% genes of the assayed genes were differentially expressed in BRF-55T as compared to BPH with symptoms tissue.

Example 4 Cluster Analysis of Up- or Down-Regulated Genes in BPH

[0117] Cluster analysis of the expression results from a large number of genes is often problematic due to variations in the standardization of the gene expression data. To compensate for these variations, a subset of differentially expressed genes was selected by a modified analysis procedure.

[0118] In a first step, a gene list comparing normal vs. disease samples was generated by two kinds of comparisons. First, genes were selected that displayed a greater than or equal to mean 2-fold up or down regulation using average difference expression values and with p<0.05. Second, genes were selected by ANOVA comparing the normal group of samples with the disease group and with a t value of >3 in the up or down direction. These lists were then combined to create an expression profile characteristic of normal controls and one characteristic of disease in which specific genes are found to be up or down regulated in disease when compared with normal controls.

[0119] In preparation for clustering analysis to identify subgroups of genes that show statistically similar expression patterns, average difference values for the selected genes were normalized across all samples (normal and disease combined) using the following formula:

Normalization data=(X−Xmean)/Sx

[0120] where Sx is variance (:STD)

[0121] This converts the mean expression value for each gene to 0 and the high and low values to 1 and −1, respectively. Thus, genes with high absolute expression values when compared with genes with low absolute expression values would not skew the comparisons when clustering algorithms are applied. The measurement of the cluster space distance was determined by using the correlation coefficient (1-r) method and clustering was performed using Ward's method (Ward, J. H. (1963) Journal of American Statistical Association, 58. 236.)

[0122] The clustering was validated by observing whether multiple elements representing the same genes showing the same direction of expression change (i.e., either up or down) tend to cluster together. To test this standardization and clustering protocol, the expression levels for genes that are represented by more than one element on the 42K gene chip set were analyzed to determine whether the multiple elements for a single gene could be clustered together. For example, tryptase, also known as alpha tryptase or beta (tryptase II) is represented by two separate elements on the 42K human gene chip. This gene is registered with 2 different element names 41268 (5), M33493_s_at (code name, Up-170) and 26389 (3), rc_AA131322_(—s)_at (code name, Up-010).

[0123] It was found that the best analysis means for decreasing measurement errors between these two elements is by the Ward method as it gave the most consistent results when compared to other clustering methods. These analysis methods may be incorporated into software or computer readable storage media for storing a computer programmer software.

Example 5 Selection of 60 Marker Genes

[0124] A panel of 60 representative marker genes (listed in Table 5) out of 400 marker genes listed in Tables 3 and 4 can be used in the assays and methods of the invention. The 60 marker genes were selected based on following criteria: (1) expression level is changed greatly in BPH patient samples compared with normal samples; (2) variation of expression levels within BPH samples and within normal samples is small; and (3) expression levels resembling BPH with symptoms are detected in cell line BRF-55T.

Example 6 Gene Expression Analysis of Select Genes

[0125] The expression levels of three genes from Tables 1-5 (the genes encoding cellular retinol binding protein, S100 calcium binding protein and PSMA) were assayed in various tissues and prostate samples by PCR as described in Example 7 (see FIGS. 1-6). Each sample was assayed for the level of GAPDH and mRNA corresponding to cellular retinol binding protein, S100 calcium binding protein or PSMA. As seen in FIGS. 1-6, these three genes are differentially regulated or expressed in BPH tissue from patients with or without symptoms and from BPH tissue from patients with prostate cancer (compared to normal prostate tissue). All three genes are therefore useful markers in the assays of the invention, such as the assays to measure the effect of an agent on BPH or the assays to detect or diagnose the occurrence or progression of BPH.

Example 7 Drug Screening Assays

[0126] The expression profiles for normal controls and disease samples described above can be used to identify compound hits from a compound library. A hit may be, but is not necessarily, defined as one of three kinds of results:

[0127] 1) The expression of an individual gene is changed in the direction of normal (i.e., if UP in disease, then down-hit, if down in disease, then up=hit). The stronger the modulation of an individual gene to a normnal phenotype, the stronger the hit status for the compound against that gene.

[0128] 2) The expression of genes that sub cluster together is evaluated for an overall pattern of modulation to a normal expression profile. The more genes in a subcluster that are modulated to a normal phenotype, the stronger the hit status for the compound against that subcluster. A subcluster may represent common or interacting cellular pathways.

[0129] 3) The overall expression profile of all of the genes being screened is evaluated for modulation to normal. The more genes that are modulated to a normal phenotype, the stronger the hit status for the compound against the entire gene set.

[0130] As described above, if a compound modulates the gene expression pattern of the screening system cells more towards any disease phenotype, then it can be used as a molecular probe to find binding proteins and/or define disease-associated cellular pathways.

[0131] As an example, candidate agents and compounds are screened for their ability to modulate the expression levels of cellular retinol binding protein, S100 calcium binding protein and PSMA by exposing a prostate cell line or cell line from BPH tissue to the agent and assaying the expression levels of these genes by real time PCR. Real time PCR detection is accomplished by the use of the ABI PRISM 7700 Sequence Detection System. The 7700 measures the fluorescence intensity of the sample each cycle and is able to detect the presence of specific amplicons within the PCR reaction. Each sample is assayed for the level of GAPDH and mRNA corresponding to cellular retinol binding protein, S100 calcium binding protein and PSMA. GAPDH detection is performed using Perkin Elmer part#402869 according to the manufacturer's directions. Primers were designed for the three genes by using Primer Express, a program developed by PE to efficiently find primers and probes for specific sequences ((1) N91971-FAM PROBE Forward: 5′-CAT ggC TTT gTT TTA AgA AAA ggA A-3′; Reverse: 5′-AgC CAC CCC CAg gCA T-3′; Probe: 5′-FAM-AgT gAC AAA gCC AAg AgA CAg ACT CTg CTA ACA-TAMRA-3′; (2) X65614-SYBR; Forward: 5′-AAA gAC AAg gAT gCC gTg gAT-3′; Reverse 5′-AgC CAC gAA CAC gAT gAA CTC-3′; (3) M99487-SYB; Forward 5′-Tgg CTC AgC ACC ACC Aga T-3′; Reverse: 5′-TTC Cag TAA AgC Cag gTC CAA-3′)

[0132] These primers are used in conjunction with SYBR green (Molecular Probes), a nonspecific double stranded DNA dye, to measure the expression level mRNA corresponding to the genes, which is normalized to the GAPDH level in each sample.

[0133] Normalized expression levels from cells exposed to the agent are then compared to the normalized expression levels in control cells. Agents that modulate the expression of one or more the genes may be further tested as drug candidates in appropriate BPH in vitro or in vivo models.

Example 8 Comparative Assays

[0134] The expression of a panel of marker genes was compared, in the same subjects as disclosed in Example 2, in a pairwise fashion between the BPH patients with (BPHWS) or without (BPHNoS) symptoms versus normal (Normal) controls and asymptomatic BPH patients with cancer (Cancer). In every case, the tissue was excised from the junction between the ejaculatory duct and the prostatic urethra in the transition zone of the prostate. In particular, BPH tissue from patients with early stage prostate cancer was carefully excised away from the cancer lesion macroscopically, and their histological diagnosis was confirmed microscopically.

[0135] Pairwise comparisons between the subject groups were subjected to an Analysis of Variance (ANOVA) model. P-values corresponding to each of six possible pairwise comparisons among the four sample groups were then determined for each gene. Table 6 depicts Affymetrix fragments, along with their GenBank accession number, which have p<0.001 for two or more of the pairwise comparisons.

[0136] A Principal Component Analysis (PCA) was performed to show that this gene set serves as a basis to discriminate among the various groups of samples. The samples are plotted using the scores for the first three principal components. Each of the four sample groups can be clearly distinguished from one another in this analysis (FIG. 7A). Component 1 (36% of the variability) discriminates between Normal and asymptomatic BPH versus BPH cancer and symptomatic BPH. Component 2 (10% of the variability) distinguishes Normal from asymptomatic BPH, and Component 3 (8% of the variability) distinguishes BPH cancer from symptomatic BPH.

[0137]FIG. 7B shows a two-dimensional representation of the PCA, with Component 1 plotted against Components 2+3. Each of the four sample groups is clustered in a different quadrant of this figure. Within each sample group, there does not appear to be any age-related clustering of samples. Further, since there is an overlap of ages between the samples groups, it does not appear that age was a confounding factor for the analysis based on this gene set. Because BPH is perceived as a natural consequence of aging, two subgroups of normal individuals were initially identified. A ‘younger’ set included individuals ranging in age from 13-20 years while the ‘older’ set ranged from 31-51 years. However, because the two subsets appeared to be indistinguishable at the molecular level, they were grouped together and in all subsequent analysis referred to as ‘Normal’ group.

[0138] Another finding was that the intra-group variability (i.e., the tightness of clustering) differed between the four groups (FIG. 7A). Normal patients exhibited the least intra-group variability, followed by asymptomatic BPH and symptomatic BPH with BPH cancer patients exhibiting the most patient-to-patient variability. On the other hand, with regard to the inter-group variation, the asymptomatic BPH group appeared to be more similar to the normal group than to symptomatic BPH (FIG. 7B).

[0139] Asymptomatic BPH samples were obtained from individuals that died from other causes and had no records of being treated for BPH but had histological evidence for BPH when examined retrospectively. Since asymptomatic samples clearly exhibit the BPH phenotype at the microscopic level, one would expect the two BPH groups to exhibit more similarity than disparity. Similarly, that the BPH cancer group is distinct from asymptomatic BPH but is more similar to the symptomatic BPH group (FIG. 7B). Since transition zone tissue from patients with prostate cancer with no clinical symptoms of BPH was analyzed from these patients, this group of patients would be expected to appear similar to normal or asymptomatic BPH. The fact that the BPH cancer group can be distinguished from every other group is also an unexpected finding. Subsequent to this PCA, additional samples were studied to extend these findings. These included two normals and three symptomatic BPH patients. Using the same set of genes, a PCA was performed with these additional samples. In FIG. 7C, the two new normal (Norm) samples group with the previous normal samples and the three new symptomatic BPH (BPH) samples group with the other symptomatic BPH samples.

Example 9 Diagnostic Assays

[0140] The expression profiles or one or more of the individual genes of Tables 1-6 are used as molecular or diagnostic markers to evaluate the disease status of a patient sample. In one embodiment, a patient prostate tissue sample is processed as described herein to produce total a cellular or mRNA. The RNA is hybridized to a chip continuing probes that specifically hybridize to one or more, or two or more of the genes in Tables 1-6. The overall expression profile generated, or the expression levels of individual genes are then compared to the profiles as described in Tables 1-6 to determine the disease or hyperplastic state of the patient sample.

[0141] Although the present invention has been described in detail with reference to examples above, it is understood that various modifications can be made without departing from the spirit of the invention. Accordingly, the invention is limited only by the following claims. All cited patents, applications, GenBank Accession numbers and publications referred to in this application are herein incorporated by reference in their entirety. TABLE 1 Normal1-Normal2 vs BPH-With Symptoms Fold- change SEQ ID N1-N2 vs p-value Affymetrix element NO: Genbank ID Genbank Name With N1-N2 vs With Up- RC_AA410383_at 277 AA410383 B-cell-homing chemokine (ligand for 22.5 0.025197485 regulated Burkitt's lymphoma receptor-1)4q21 RC_AA463726_s_at 386 AA463726 JM27 proteinXp11.23 14.9 0.018598344 RC_AA057195_at 47 AA057195 Homo sapiens mRNA; cDNA 14.0 0.029325045 DKFZp586M121 (from clone DKFZp586M121) V01512_rna1_at 993 V01512 v-fos FBJ murine osteosarcoma viral 13.1 0.001027561 oncogene homolog14q24.3 RC_AA427622_s_at 311 AA427622 collagen, type XIII, alpha 110q22 11.6 0.00074954 RC_N23730_s_at 724 N23730 v-fos FBJ murine osteosarcoma viral 11.4 0.000631487 oncogene homolog14q24.3 RC_AA465491_at 391 AA465491 Mad4 homolog4p16.3 11.4 0.031024189 RC_AA620825_at 454 AA620825 ESTs 11.3 0.010915901 RC_R93908_at 865 R93908 ESTs 11.3 0.019994337 RC_AA461300_at 381 AA461300 ESTs 11.0 0.007061759 N40141_at 743 N40141 JM27 proteinXp11.23 10.9 0.013756347 RC_R25410_at 814 R25410 ESTs 7.7 0.01851753 L49169_at 649 L49169 FBJ murine osteosarcoma viral 7.4 0.041523744 oncogene homolog B19q13.3 RC_AA279760_at 193 AA279760 ESTs 7.0 0.024411468 RC_T90889_at 927 T90889 ESTs 6.5 0.015666863 U62015_at 978 U62015 insulin-like growth factor binding 6.0 0.002843661 protein 101p22-p31 RC_AA188981_at 112 AA188981 highly expressed in cancer, rich in 5.9 0.002280479 leucine heptad repeats D83018_at 513 D83018 nel (chicken)-like212q13.11-q13.12 5.6 0.000570952 RC_H64493_f_at 590 H64493 immunoglobulin gamma 3 (Gm 5.6 0.01109802 marker)14q32.33 X52541_at 1064 X52541 early growth response 15q31.1 5.2 0.002428259 M57466_s_at 690 M57466 major histocompatibility complex, 5.1 0.002137399 class II, DP beta 16p21.3 J03507_at 621 J03507 complement component 75p13 4.9 1.36616E−05 RC_N30198_at 733 N30198 ESTs 4.8 0.003366461 RC_T78398_at 913 T78398 EST 4.8 0.033293747 RC_H17550_at 559 H17550 ESTs 4.7 0.047828622 RC_T67053_f_at 909 T67053 immumoglobulin lambda gene 4.5 0.045107075 cluster22q11.1-q11.2 RC_AA598982_s_at 429 AA598982 trophininXp11.22-p11.21 4.3 0.000902336 RC_AA256268_at 175 AA256268 ESTs 4.2 0.001506239 HG3543-HT3739_at 675 M29645 insulin-like growth factor 2 4.1 0.017253126 (somatomedin A)11p15.5 RC_N91971_f_at 791 N91971 retinol-binding protein 1, cellular3q23 4.1 0.02528773 RC_AA479286_at 403 AA479286 ESTs 4.0 0.028009544 M62831_at 695 M62831 immediate early protein19 4.0 0.000484086 RC_F02992_at 526 F02992 ESTs, Weakly similar to unknown 3.9 0.031845412 [M. musculus] RC_H86112_f_at 600 H86112 KIAA0471 geneproduct1q24-q25 3.8 0.004155259 RC_AA436616_at 335 AA436616 ESTs 3.8 0.017156387 RC_T62857_at 903 T62857 ESTs 3.7 0.000301735 RC_AA281345_f_at 201 AA281345 immediate early protein19 3.6 0.001679723 U21128_at 953 U21128 lumican12q21.3-q22 3.6 2.19529E−05 U30521_at 960 U30521 P311 protein 3.6 0.001150397 RC_N58172_at 757 N58172 ESTs 3.5 0.043092144 RC_T03229_f_at 874 T03229 EST 3.5 0.031101935 Up- RC_AA410383_at 277 AA410383 B-cell-homing chemokine (ligand for 22.5 0.025197485 regulated Burkitt's lymphoma receptor-1)4q21 X06700_s_at 1049 X06700 collagen, type III, alpha 1 (Ehlers- 3.5 0.008472599 Danlos syndrome type IV, autosomal dominant)2q31 RC_Z39904_at 1111 Z39904 Homo sapiens clone 23555 mRNA 3.4 0.002949046 sequence RC_T23622_at 886 T23622 ESTs 3.4 0.002174281 J00231_f_at 617 J00231 immunoglobulin gamma 3 (Gm 3.4 0.009322568 marker)14q32.33 RC_AA028092_s_at 17 AA028092 transcription factor 216pter-qter 3.4 3.13963E−06 RC_AA252528_at 170 AA252528 ESTs 3.4 0.000225707 L33799_at 645 L33799 procollagen C-endopeptidase 3.3 0.018469201 enhancer7q22 RC_F09748_s_at 537 F09748 Homo sapiens mRNA; cDNA 3.2 0.02728166 DKFZp586K1220 (from clone DKFZp586K1220) RC_T64223_s_at 907 T64223 carboxypeptidase A3 (mast cell)3q21 3.2 0.027915742 q25 RC_AA402903_f_at 263 AA402903 immunoglobulin gamma 3 (Gm 3.2 0.044721116 marker)14q32.33 RC_F13763_at 542 F13763 ESTs 3.1 0.000503701 RC_AA488432_at 412 AA488432 phosphoserine phosphatase7p21- 3.1 0.020997503 p15 RC_AA486072_i_at 410 AA486072 small inducible cytokine A5 3.1 0.025877597 (RANTES)17q11.2-q12 RC_N22006_s_at 719 N22006 EST 3.1 0.00148561 RC_AA257093_r_at 178 AA257093 T-cell receptor, beta cluster7q35 3.1 1.71945E−07 RC_AA609943_at 449 AA609943 ESTs 3.0 0.029360518 RC_T23490_s_at 885 T23490 ESTs 3.0 0.008741411 D13628_at 476 D13628 angiopoietin 18q22.3-q23 2.9 0.006228419 M73720_at 702 M73720 carboxypeptidase A3 (mast ceLl)3q21 2.9 0.006585391 q25 Z74616_s_at 1123 Z74616 collagen, type I, alpha 27q22.1 2.8 0.008750622 AA082546_at 54 AA082546 ESTs 2.8 0.019771126 RC_AA284920_at 213 AA284920 ESTs 2.7 0.019738239 RC_AA599365_at 434 AA599365 decorin12q23 2.7 0.001295936 X57025_at 1066 X57025 insulin-like growth factor 1 2.7 0.022341194 (somatomedin C)12q22-q23 X51345_at 1062 X51345 jun B proto-oncogene19p13.2 2.7 0.036487159 RC_N67876_s_at 773 N67876 insulin-like growth factor 1 2.7 0.035216134 (somatomedin C)12q22-q23 RC_AA609504_at 444 AA609504 KIAA0405 gene product 2.7 0.020881055 RC_N69207_at 776 N69207 ESTs, Moderately similar to !!!! ALU 2.6 0.041315387 SUBFAMILY SB2 WARNING ENTRY !!!! [H. sapiens ] M87789_s_at 704 M87789 immunoglobulin gamma 3 (Gm 2.6 0.038916248 marker)14q32.33 HG3510-HT3704_at 1055 X12795 nuclear receptor subfamily 2, group 2.6 0.016151338 F, member 15q14 RC_T64211_at 906 T64211 ESTs, Weakly similar to pancortin-1 2.6 0.006233291 8 M. musculus] U90552_s_at 988 U90552 butyrophilin, subfamily 3, member 2.6 0.004564282 A16p23 M34516_r_at 684 M34516 immunoglobulin lambda-like 2.6 0.049767038 polypeptide 322q11.2 Up- RC_AA410383_at 277 AA410383 B-cell-homing chemokine (ligand for 22.5 0.025197485 regulated Burkitt's lymphoma receptor-1)4q21 RC_T23468_at 884 T23468 ESTs 2.5 0.00250737 RC_AA173223_at 108 AA173223 ESTs, Weakly similar to !!!! ALU 2.5 0.007080285 SUBFAMILY SQ WARNING ENTRY !!!! [H. sapiens ] RC_T49061_at 894 T49061 ESTs 2.5 0.039642391 RC_AA234095_at 144 AA234095 ESTs 2.5 0.003152859 RC_F01920_s_at 520 F01920 pre-B-cell leukemia transcription 2.5 0.002088945 factor 39q33-q34 RC_N91461_at 789 N91461 ESTs 2.4 0.01015467 RC_N67575_s_at 771 N67575 osteoglycin (osteoinductive factor) 2.4 0.004044061 RC_AA151210_at 89 AA151210 ESTs 2.4 0.011476541 AA156897_s_at 97 AA156897 Homo sapiens mRNA; cDNA 2.4 0.033974981 DKFZp564I1922 (from clone DKFZp564I1922) W73859_at 1028 W73859 transcription factor 216pter-qter 2.4 0.024640626 RC_H68097_at 592 H68097 EST 2.4 0.04870874 RC_AA436618_at 336 AA436618 ESTs 2.4 0.02483165 M33493_s_at 680 M33493 tryptase, beta (tryptase II)16p13.3 2.4 0.02689938 AB002340_at 461 AB002340 KIAA0342 gene product 2.3 0.000748796 RC_AA446661_at 347 AA446661 ESTs 2.3 0.011980248 RC_AA084138_at 55 AA084138 ESTs 2.3 1.16025E−05 RC_N59866_at 761 N59866 ESTs, Weakly similar to putative 2.3 0.002042263 p150 [H. sapiens ] RC_R42424_at 832 R42424 ESTs 2.3 0.003173074 RC_N39415_at 742 N39415 osteoglycin (osteoinductive factor) 2.3 0.001310764 J03464_s_at 620 J03464 collagen, type I, alpha 27q22.1 2.3 0.006791534 RC_AA205376_at 121 AA205376 KIAA0471 gene product1q24-q25 2.3 0.023123837 RC_H95960_at 606 H95960 secreted protein, acidic, cysteine-rich 2.3 0.008509182 (osteonectin)5q31.3-q32 D28137_at 484 D28137 bone marrow stromal cell antigen 2.3 0.031127266 219p13.2 RC_N79778_at 784 N79778 extracellular matrix protein 2, female 2.3 0.045073744 organ and adipocyte specific9q22.3 RC_N98485_s_at 800 N98485 forkhead (Drosophila)-like 66p25.3 2.3 0.033372862 M98539_at 715 M98539 prostaglandin D2 synthase (21 kD, 2.2 0.005442674 brain)9q34.2-q34.3 RC_AA205724_at 123 AA205724 ESTs 2.2 0.006183612 U85625_at 986 U85625 Homo sapiens ribonuclease 6 2.2 0.001245066 precursor, mRNA, complete cds. RC_R37588_s_at 821 R37588 RAB2, member RAS oncogene 2.2 0.00219386 family-like6p21.3 RC_AA046426_at 35 AA046426 Cdc42 effector protein 3 2.2 0.005788723 RC_AA256294_at 176 AA256294 ESTs 2.2 0.002425605 RC_AA599120_at 431 AA599120 SWI/SNF related, matrix associated, 2.2 0.04 2979241 actin dependent regulator of chromatin, subfamily e, member 1 RC_W60186_at 1018 W60186 ESTs 2.2 0.028494835 RC_AA599216_at 432 AA599216 collapsin response mediator protein 2.2 0.040523744 14p16.1-p15 RC_AA450324_at 360 AA450324 ESTs 2.1 0.009094567 M31994_at 678 M31994 Homo sapiens aldehyde 2.1 0.001561218 dehydrogenase (ALDH1) gene Up- RC_AA410383_at 277 AA410383 B-cell-homing chemokine (ligand for 22.5 0.025197485 regulated Burkitt's lymphoma receptor-1)4q21 RC_AA402930_at 264 AA402930 ESTs 2.1 0.000114627 M91029_cds2_at 706 M91029 Human AMP deaminase isoform L 2.1 0.02494373 (AMPD2) mRNA, exons 6-18, partial cds RC_AA450114_at 358 AA450114 ESTs, Weakly similar to 17beta- 2.1 4.87556E−06 hydroxysteroid dehydrogenase [H. sapiens ] D62584_at 501 D62584 osteoglycin (osteoinductive factor) 2.1 0.000157116 RC_AA621634_at 457 AA621634 ESTs 2.1 0.02297009 RC_AA312946_s_at 228 AA312946 ESTs 2.1 3.51075E−05 X07438_s_at 1054 X07438 Human DNA for cellular retinol 2.1 0.039015947 binding protein (CRBP) RC_N53447_at 751 N53447 integral membrane protein 2CXq21.1- 2.1 0.009032297 21.2 RC_AA281591_at 202 AA281591 Homo sapiens mRNA; cDNA 2.0 0.016660714 DKFZp586B211 (from clone DKFZp586B211) RC_R71395_at 854 R71395 ESTs, Moderately similar to 2.0 0.046231847 alternatively spliced product using exon 13A [H. sapiens ] RC_T53590_s_at 899 T53590 cytochrome P450, subfamily XIA 2.0 0.00282074 (cholesterol side chain cleavage)15q23-q24 RC_AA293489_at 224 AA293489 KIAA0638 protein 2.0 0.006966532 RC_AA447707_s_at 351 AA447707 KIAA1055 protein 2.0 0.001248537 RC_AA235618_f_at 149 AA235618 ESTs 2.0 0.012481746 RC_N68350_at 775 N68350 ESTs 2.0 0.035156598 RC_H81379_s_at 596 H81379 ESTs, Moderately similar to 2.0 0.01148429 KIAA0438 [H. sapiens ] RC_D51060_s_at 495 D51060 Jun activation domain binding 2.0 0.016668951 protein1p32-p31 U72649_at 983 U72649 B-cell translocation gene 2 2.0 0.020660388 (pheochromacytoma cell-3)1q32 RC_AA287389_at 216 AA287389 ESTs 2.0 0.002741873 RC_AA621367_at 456 AA621367 ESTs 2.0 0.004871903 J03040_at 619 J03040 secreted protein, acidic, cysteine-rich 2.0 0.006303994 (osteonectin)5q31.3-q32 RC_AA291676_s_at 219 AA291676 non-metastatic cells 5, protein 2.0 0.027480479 expressed in (nucleoside- diphosphate kinase)5q23-q31 RC_N63536_at 763 N63536 ESTs 2.0 0.000634305 RC_AA411952_at 282 AA411952 UDP-Gal:betaGlcNAc beta 1,3- 2.0 0.011858934 galactosyltransferase, polypeptide 33q25 RC_AA252802_s_at 171 AA252802 Human mRNA for TI-227H 2.0 0.041027635 RC_AA382275_at 244 AA382275 ESTs 2.0 0.00087437 AA093923_at 63 AA093923 tissue inhibitor of metalloproteinase 2.0 0.046200886 217q25 M11313_s_at 654 M11313 alpha-2-macroglobulin12p13.3-p12.3 2.0 0.013660595 RC_AA398280_at 248 AA398280 ESTs 2.0 0.044320644 RC_N51529_at 747 N51529 ESTs 2.0 0.006276979 H49440_at 578 H49440 nudix (nucleoside diphosphate linked 2.0 0.013879331 moiety X)-type motif 36p21.2 Up- RC_AA410383_at 277 AA410383 B-cell-homing chemokine (ligand for 22.5 0.025197485 regulated Burkitt's lymphoma receptor-1)4q21 RC_T33263_s_at 890 T33263 KIAA0320 protein 2.0 0.009994615 RC_T89160_r_at 921 T89160 ESTs 2.0 0.005289266 RC_W56792_at 1016 W56792 ESTs, Weakly similar to 2.0 0.026130523 serine/threonine protein kinase TAO1 8 R. norvegicus] RC_R60056_at 849 R60056 ESTs, Moderately similar to 2.0 0.001585076 alternatively spliced product using exon 13A [H. sapiens ] Down- RC_AA398908_at 251 AA398908 Human Chromosome 16 BAC clone −21.7 0.007918174 regulated CIT987SK-A-61E3 RC_AA460914_at 380 AA460914 ESTs −15.8 0.013659536 RC_T40895_at 892 T40895 ESTs −12.6 0.002430219 RC_R71792_s_at 855 R71792 ESTs, Moderately similar to FAT- −9.8 0.01438632 SPECIFIC PROTEIN FSP27 8 M. musculus] RC_N80129_i_at 785 N80129 metallothionein 1L16q13 −8.7 0.002816872 X66141_at 1078 X66141 myosin, light polypeptide 2, −8.0 0.03928942 regulatory, cardiac, slow12q23-q24.3 AA234634_f_at 145 AA234634 CCAAT/enhancer binding protein −7.4 0.000589696 (C/EBP), delta8p11.2-p11.1 U78294_at 985 U78294 arachidonate 15-lipoxygenase, −6.8 0.017271608 second type RC_AA457566_at 375 AA457566 ESTs −6.6 0.029644622 X93036_at 1093 X93036 phospholemman-like, expressed in −6.2 0.011323909 breast tumors, 8kD X57129_at 1067 X57129 H1 histone family, member 26p21.3 −6.1 0.004161922 HG1067-HT1067_r_at 671 M22406 Human intestinal mucin mRNA, −5.8 0.007202185 partial cds, clone SMUC 42 X65614_at 1076 X65614 S100 calcium-binding protein P4p16 −5.8 0.006892572 RC_AA609006_at 440 AA609006 ESTs −5.7 0.015701354 J03910_rna1_at 622 J03910 metallothionein 1G16q13 −5.7 0.003506953 RC_H94471_at 604 H94471 occludin5q13.1 −5.6 0.025014274 AB000584_at 459 AB000584 prostate differentiation factor −5.4 0.003235425 RC_W88568_at 1035 W88568 glycogenin 2Xp22.3 −5.1 0.048573115 V00594_at 992 V00594 metallothionein 2A16q13 −5.0 0.000721258 RC_T73433_s_at 912 T73433 angiotensinogen1q41-qter −4.9 0.012700144 RC_N94303_at 797 N94303 ESTs −4.5 4.88059E−05 RC_AA419011_at 296 AA419011 Homo sapiens mRNA; cDNA −4.1 0.013801595 DKFZp586D0823 (from clone DKFZp586D0823) RC_N32748_at 736 N32748 ESTs −4.1 0.018749207 RC_AA053424_at 40 AA053424 ESTs, Weakly similar to mucin Muc3 −4.0 0.001235197 [R. norvegicus] RC_AA599331_at 433 AA599331 ESTs −4.0 0.005480655 M99487_at 716 M99487 folate hydrolase (prostate-specific −3.9 0.013268152 membrane antigen) 111p11.2 RC_F02245_at 522 F02245 monoamine oxidase AXp11.4-p11.3 −3.8 0.002950391 X76717_at 1087 X76717 metallothionein 1L16q13 −3.7 0.000868707 Up- RC_AA410383_at 277 AA410383 B-cell-homing chemokine (ligand for 22.5 0.025197485 regulated Burkitt's lymphoma receptor-1)4q21 X64177_f_at 1075 X64177 metallothionein 1H16q13 −3.7 0.002089771 RC_AA599522_r_at 437 AA599522 squamous cell carcinoma antigen −3.6 0.012643918 recognised by T cells L77701_at 651 L77701 human homolog of yeast −3.6 0.003341007 mitochondrial copper recruitment gene RC_D11824_at 474 D11824 ESTs, Moderately similar to weak −3.6 0.000803294 similarity to Arabidopsis thaliana ubiquitin-like protein 8 [C. elegans] RC_AA410311_at 275 AA410311 ESTs −3.5 0.001234064 RC_AA457235_at 373 AA457235 ESTs −3.5 0.012177965 RC_N93798_at 796 N93798 protein tyrosine phosphatase type −3.5 0.007340453 IVA, member 3 RC_AA416762_s_at 291 AA416762 nuclear receptor subfamily 1, group −3.5 0.010404304 H, member 219q13.3-19q13.3 RC_F03969_at 528 F03969 ESTs, Weakly similar to tumorous −3.5 0.011826812 imaginal discs protein Tid56 homolog [H. sapiens ] RC_AA045487_at 31 AA045487 ESTs −3.4 0.025187615 RC_Z38744_at 1108 Z38744 putative gene product13 −3.4 2.30674E−05 RC_N92502_s_at 794 N92502 ESTs, Moderately similar to HERV-E −3.4 0.02301359 integrase [H. sapiens ] RC_R91484_at 863 R91484 ESTs −3.4 8.2306E−05 RC_AA165313_at 104 AA165313 ESTs −3.3 0.028364404 RC_AA182030_at 110 AA182030 ESTs −3.3 0.019770486 RC_T94447_s_at 928 T94447 ESTs, Moderately similar to (defline −3.3 0.001427294 not available 4335935) [M. musculus] RC_W20486_f_at 995 W20486 ESTs −3.3 0.002892697 RC_R16983_at 811 R16983 ESTs −3.2 0.000912559 RC_AA504805_s_at 424 AA504805 interferon stimulated gene −3.2 0.003905701 (20kD)15q26 RC_T90190_s_at 925 T90190 H1 histone family, member 26p21.3 −3.2 0.020618793 RC_AA135870_at 79 AA135870 ESTs −3.1 0.04609197 RC_H99035_at 612 H99035 ESTs −3.1 0.000191451 RC_R28370_at 815 R28370 ESTs −3.1 0.024606319 RC_T40995_f_at 893 T40995 alcohol dehydrogenase 3 (class I), −3.1 0.024064044 gamma polypeptide4q21-q23 MIP1-B_at 1124 M35590 karyopherin (importin) beta 2 −3.1 0.005882353 RC_AA447522_at 349 AA447522 ESTs, Highly similar to differentially −3.1 0.003518059 expressed in Fanconi anemia [H. sapiens ] RC_AA461453_at 382 AA461453 ESTs, Moderately similar to Cab45a −3.0 0.021949087 [M. musculus] AA429539_f_at 318 AA429539 ESTs −3.0 0.017623102 RC_AA476944_at 394 AA476944 ESTs −3.0 0.019974254 RC_N80129_f_at 785 N80129 metallothionein 1L16q13 −3.0 0.000219038 RC_N26904_at 731 N26904 ESTs, Weakly similar to −2.9 0.006305062 FK506/rapamycin-binding protein FKBP13 precursor [H. sapiens ] RC_AA505136_at 426 AA505136 ESTs −2.9 0.005400284 AA455001_s_at 368 AA455001 ESTs −2.9 2.1534E−05 RC_W70131_at 1024 W70131 ESTs −2.9 0.005764635 Up- RC_AA410383_at 277 AA410383 B-cell-homing chemokine (ligand for 22.5 0.025197485 regulated Burkitt's lymphoma receptor-1)4q21 RC_AA043349_at 27 AA043349 ESTs −2.9 0.016983419 U02020_at 936 U02020 pre-B-cell colony-enhancing factor −2.9 0.003324497 U52969_at 970 U52969 Purkinje cell protein 421q22.2-q22.3 −2.8 0.00078638 RC_H22453_at 564 H22453 ESTs −2.8 0.000410695 RC_N22620_at 722 N22620 ESTs −2.8 0.005507089 RC_N64683_at 764 N64683 ESTs −2.8 0.00378977 RC_N24761_at 725 N24761 ESTs −2.8 0.004837185 RC_AA464728_s_at 388 AA464728 ESTs −2.8 0.004669897 RC_H83380_at 598 H83380 ESTs −2.7 0.016543793 M30894_at 676 M30894 T-cell receptor, gamma cluster7p15- −2.7 0.034153167 p14 RC_H81070_f_at 595 H81070 Human metallothionein (MT)I-F gene −2.7 0.022654931 J00073_at 615 J00073 actin, alpha, cardiac muscle15q11- −2.7 0.029724167 qter RC_H05084_at 547 H05084 ESTs, Weakly similar to ORF −2.7 0.016965435 YDL055c [S. cerevisiae] AA045870_at 34 AA045870 Homo sapiens mRNA; cDNA −2.7 0.005480167 DKFZp564A072 (from clone DKFZp564A072) RC_T68873_f_at 911 T68873 metallothionein 1L16q13 —2.7 0.001140431 RC_N72253_at 778 N72253 ESTs −2.7 0.001832591 RC_AA447977_s_at 352 AA447977 Homo sapiens mRNA; cDNA −2.7 0.001255304 DKFZp564A072 (from clone DKFZp564A072) RC_H18947_at 561 H18947 ESTs −2.7 0.00193501 RC_H77597_f_at 594 H77597 metallothionein 1H16q13 −2.7 0.001560766 RC_H94475_s_at 605 H94475 alpha-2-plasmin inhibitor17pter-p12 −2.6 0.01435663 RC_AA025370_at 15 AA025370 KIAA0872 protein −2.6 0.013924142 RC_AA443114_at 343 AA443114 ESTs, Moderately similar to PIM-1 −2.6 0.000703574 PROTO-ONCOGENE SERINE/THREONINE-PROTEIN KINASE [M. musculus] RC_F09684_at 535 F09684 ESTs −2.6 0.000107291 RC_AA031360_s_at 20 AA031360 ESTs −2.6 0.047293081 RC_AA416685_at 290 AA416685 UNC13 (C. elegans)-like9p11-p12 −2.6 0.023296279 D29805_at 487 D9805 UDP-Gal:betaGlcNAc beta 1,4- −2.6 2.3562E−05 galactosyltransferase, polypeptide 19p13 RC_H58873_s_at 583 H58873 solute carrier family 2 (facilitated −2.5 0.000710917 glucose transporter), member 11p35- p31.3 M10942_at 652 M10942 metallothionein 1E (functional)16q13 −2.5 0.017370635 RC_T03593_at 875 T03593 ESTs −2.5 0.006239127 RC_N95495_at 799 N95495 small inducible cytokine A5 −2.5 0.002392984 (RANTES)17q11.2-q12 RC_AA017063_r_at 8 AA017063 ESTs, Highly similar to Miz-1 protein −2.5 0.048093776 [H. sapiens ] RC_R00144_at 801 R00144 ESTs −2.5 0.018222161 RC_AA599522_f_at 437 AA599522 squamous cell carcinoma antigen −2.5 0.03100833 recognised by T cells Up- RC_AA410383_at 277 AA410383 B-cell-homing chemokine (ligand for 22.5 0.025197485 regulated Burkitt's lymphoma receptor-1)4q21 RC_AA219552_s_at 134 AA219552 ESTs −2.5 0.043156485 RC_AA447537_at 350 AA447537 ESTs, Moderately similar to (define −2.5 0.031129269 not available 5360237) [M. musculus] RC_AA070752_s_at 51 AA070752 insulin receptor substrate 12q36 −2.5 0.002895462 RC_R02003_r_at 804 R02003 ESTs, Weakly similar to cappuccino −2.4 0.002315115 [D. melanogaster] L13698_at 638 L13698 growth arrest-specific 19q21.3-q22.1 −2.4 0.013393145 RC_AA432292_at 325 AA432292 ESTs, Moderately similar to B cell −2.4 0.000956642 growth factor [H. sapiens ] RC_H99648_s_at 613 H99648 DNA segment, single copy probe −2.4 0.009066307 LNS-CAI/LNS-CAII (deleted in polyposis5q22-q23 RC_AA131919_at 75 AA131919 putative type II membrane protein −2.4 0.000187872 RC_AA621695_at 458 AA621695 ESTs −2.4 0.008761556 RC_AA598695_at 427 AA598695 ESTs, Weakly similar to !!!! ALU −2.4 0.000549977 SUBFAMILY SX WARNING ENTRY !!!! [H. sapiens ] RC_AA430388_at 321 AA430388 ESTs, Moderately similar to !!!! ALU −2.4 0.000135176 SUBFAMILY SQ WARNING ENTRY !!!! [H. sapiens ] M24069_at 672 M24069 cold shock domain protein A12p13.1 −2.4 0.015890231 RC_AA434108_at 327 AA434108 Homo sapiens heat shock protein −2.4 0.013182623 hsp40-3 mRNA, complete cds RC_AA405488_at 268 AA405488 ESTs −2.3 0.015044159 RC_AA419546_at 297 AA419546 ESTs −2.3 0.030432017 RC_W38197_at W38197 EST −2.3 0.013006462 RC_R38709_s_at 824 R38709 superoxide dismutase 2, −2.3 0.03567491 mitochondrial6q25.3 RC_AA121142_at 69 AA121142 ESTs, Moderately similar to copper −2.3 0.043639016 transport protein HAH1 [H. sapiens ] RC_N26801_at 730 N26801 ESTs −2.3 0.000580867 RC_N75960_at 781 N75960 ESTs −2.3 0.01244791 RC_R36969_at 820 R36969 ESTs −2.3 0.019129486 AA046840_at 36 AA046840 CCAAT/enhancer binding protein −2.3 0.002504544 (C/EBP), delta8p11.2-p11.1 RC_R46074_at 840 R46074 transforming, acidic coiled-coil −2.3 0.003462273 containing protein 210q26 X06956_at 1051 X06956 tubulin, alpha 1 (testis specific)2q −2.3 0.015437809 RC_H84761_s_at 599 H84761 glutathione peroxidase 13p21.3 −2.2 0.000365528 RC_W52065_f_at 1012 W52065 KIAA0539 gene product −2.2 0.016497348 RC_AA279757_at 192 AA279757 ESTs, Weakly similar to (define not −2.2 0.003272622 available 4481810) [D. melanogaster] RC_H16676_s_at 556 H16676 ESTs, Weakly similar to (define not −2.2 8.86866E−05 available 5107634) 8 R. norvegicus] RC_AA255480_at 173 AA255480 ESTs −2.2 0.009359024 RC_R96924_s_at 866 R96924 ESTs −2.2 0.000201685 RC_AA342337_at 231 AA342337 ESTs, Moderately similar to !!!! ALU −2.2 0.024999347 SUBFAMILY SQ WARNING ENTRY !!!! [H. sapiens ] RC_AA004699_at 1 AA004699 putative translation initiation factor −2.2 0.022298405 Up- RC_AA410383_at 277 AA410383 B-cell-homing chemokine (ligand for 22.5 0.025197485 regulated Burkitt's lymphoma receptor-1)4q21 RC_AA401965_at 258 AA401965 tumor suppressor deleted in oral −2.2 0.006294885 cancer-related 111q13 RC_F02470_at 524 F02470 Homo sapiens clone 24796 mRNA −2.2 0.022313149 sequence X76180_at 1086 X76180 sodium channel, nonvoltage-gated 1 −2.2 0.023078001 alpha 12p13 RC_R49138_s_at 841 R49138 coatomer protein complex, subunit −2.2 0.020401578 epsilon RC_D80237_s_at 506 D80237 actin related protein 2/3 complex, −2.2 0.022022634 subunit 4 (20 kD) RC_AA402224_at 260 AA402224 growth arrest and DNA-damage- −2.2 0.014983528 inducible, gamma9q22.1-q22.2 RC_AA281599_at 203 AA281599 Homo sapiens mRNA for for histone −2.2 0.029567009 H2B, clone pjG4-5-14 RC_N78630_at 782 N78630 KIAA0870 protein −2.2 0.006668895 X85785_rna1_at 1091 X85785 Duffy blood group1q21-q22 −2.2 0.018706507 RC_AA412063_at 285 AA412063 ESTs −2.2 0.000686563 RC_AA022886_at 14 AA022886 ESTs, Weakly similar to −2.2 0.000777067 phosphatidylinositol transfer protein [H. sapiens ] RC_N24899_at 726 N24899 ESTs −2.2 0.030610964 RC_AA101767_at 66 AA101767 ESTs −2.2 0.009040467 RC_AA045503_at 32 AA045503 ESTs, Weakly similar to Homo −2.2 0.021950966 sapiens p20 protein [H. sapiens ] RC_F10078_at 538 F10078 ESTs −2.1 0.040699115 RC_H02308_at 545 H02308 ESTs −2.1 0.036730715 RC_AA284153_at 210 AA284153 ESTs −2.1 0.021270233 RC_AA453433_at 363 AA453433 HLA-B associated transcript-16p21.3 −2.1 0.013366375 RC_AA403159_at 265 AA403159 Homo sapiens Ste-20 related kinase −2.1 0.025212073 SPAK mRNA, complete cds RC_T17428_s_at 883 T17428 Homo sapiens clone 23836 mRNA −2.1 0.044754602 sequence RC_W92449_at 1037 W92449 ESTs, Highly similar to (defline not −2.1 0.019386585 available 4587714) [H. sapiens ] RC_AA609312_at 443 AA609312 ESTs −2.1 0.003204911 D28589_at 486 D28589 Human mRNA (KIAA00167), partial −2.1 0.000408478 sequence RC_AA232508_at 139 AA232508 ESTs, Highly similar to (defline not −2.1 0.004626663 available 4929647) [H. sapiens ] RC_AA280929_5_at 199 AA280929 ESTs −2.1 0.028189798 W63793_at 1020 W63793 S-adenosylmethionine decarboxylase −2.1 0.032076011 16q21-q22 RC_R36881_s_at 819 R36881 Homo sapiens DNA from −2.1 0.007343473 chromosome 19-cosmid R30879 containing USF2, genomic sequence RC_AA278767_s_at 188 AA278767 ESTs −2.1 0.001983494 RC_R98442_at 867 R98442 ESTs −2.1 0.007227226 X99728_at 1098 X99728 H. sapiens NDUFV3 gene, exon 3. −2.1 0.001404191 RC_R09379_at 807 R09379 solute carrier family 11 (proton- −2.1 0.006004344 coupled divalent metal ion transporters), member 212q13 Up- RC_AA410383_at 277 AA410383 B-cell-homing chemokine (ligand for 22.5 0.025197485 regulated Burkitt's lymphoma receptor-1)4q21 RC_R99092_at 868 R99092 EST, Moderately similar to (define −2.1 0.016256526 not available 5052951) [H. sapiens ] X95325_s_at 1095 X95325 cold shock domain protein A12p13.1 −2.1 0.025953179 RC_T56281 f_at 902 T56281 Human metallothionein (MT)I-F gene −2.1 0.032089569 RC_R44397_at 835 R44397 ESTs −2.1 0.000265391 RC_H27180_f_at 568 H27180 ESTs −2.1 0.004317675 AA165312_at 103 AA165312 ESTs −2.1 0.025559572 RC_AA279313_s_at 191 AA279313 methyl CpG binding protein 2Xq28 −2.1 0.030594523 HG4322-HT4592_at 465 AF141349 Homo sapiens beta-tubulin mRNA, −2.1 0.017120749 complete cds. RC_H81413_f_at 597 H81413 high-mobility group (nonhistone −2.1 0.009976588 chromosomal) protein isoforms I and Y6p21 RC_W94333_at 1039 W94333 ESTs, Highly similar to (define not −2.1 0.000435688 available 5107163) [H. sapiens ] RC_AA455070_at 369 AA455070 eukaryotic translation initiation factor −2.1 0.025226928 3, subunit 1 (alpha, 35kD) RC_R11526_f_at 809 R11526 parathymosin17q12-q22 −2.1 0.027182202 RC_T15409_f_at 877 T15409 EST −2.1 0.001478856 RC_H05625_f_at 548 H05625 ESTs −2.1 0.024564209 RC_AA620461_at 452 AA620461 ESTs −2.0 0.022844667 RC_AA449791_f_at 356 AA449791 EST −2.0 0.025394324 RC_AA435769_s_at 330 AA435769 ESTs −2.0 0.008375153 RC_N55502_at 755 N55502 ESTs −2.0 0.021894439 AF001294_at 463 AF001294 tumor suppressing subtransferable −2.0 0.03566128 candidate 311p15.5 RC_Z40898_at 1118 Z40898 ESTs, Highly similar to (defline not −2.0 0.002289892 available 4929639) [H. sapiens ] RC_AA436861_at 340 AA436861 ESTs −2.0 0.00187676 M63573_at 697 M63573 peptidyiprolyl isomerase B −2.0 0.044239663 (cyclophilin B)15 RC_T25732_f_at 888 T25732 KIAA0252 protein −2.0 0.041237995 RC_R01257_at 803 R01257 ESTs, Weakly similar to (defline not −2.0 0.005735841 available 4456991) [H. sapiens ] RC_H91703_i_at 603 H91703 cell division cycle 2717q12-17q23.2 −2.0 0.001412925 RC_N34817_at 739 N34817 ESTs −2.0 0.040996591 RC_R60777_at 850 R60777 ESTs, Weakly similar to KIAA0374 −2.0 0.000245565 [H. sapiens ] RC_AA386264_at 245 AA386264 ESTs, Weakly similar to −2.0 0.000541139 MICROTUBULE-ASSOCIATED PROTEIN 1B [M. musculus] RC_AA251769_at 168 AA251769 ESTs, Weakly similar to Containing −2.0 0.008985897 ATP/GTP-binding site motif A(P- loop): Similar to C. elegans protein(P1:CEC47E128);Similar to Mouse alpha- mannosidase(P1:B54407) [H. sapiens ] RC_R56602_at 846 R56602 Ig superfamily proteinXq12-q13.3 −2.0 0.024051216 RC_AA397919_at 247 AA397919 ESTs −2.0 0.029784087 Up- RC_AA410383_at 277 AA410383 B-cell-homing chemokine (ligand for 22.5 0.025197485 regulated Burkitt's lymphoma receptor-1)4q21 RC_W37778_f_at 1002 W37778 ESTs, Weakly similar to envelope −2.0 0.043013942 protein [H. sapiens ] AA248555_at 164 AA248555 ESTs −2.0 0.000824698 RC_AA463693_at 385 AA463693 ESTs, Weakly similar to −2.0 0.002809026 SERINE/THREONINE-PROTEIN KINASE NEK3 [H. sapiens ] W76181_at 1030 W76181 NADH dehydrogenase (ubiquinone) 1 −2.0 0.008370263 alpha subcomplex, 2 (8kD, B8)5q31 RC_AA171939_at 106 AA171939 ESTs −2.0 0.015796116 U30999_at 961 U30999 U30999 Homo sapiens MV3 −2.0 0.007070546 melanoma Homo sapiens cDNA clone memd RC_F03254_f_at 527 F03254 synuclein, alpha (non A4 component −2.0 0.011479379 of amyloid precursor)4q21 RC_H26288_at 567 H26288 ESTs, Weakly similar to !!!! ALU −2.0 0.000262324 SUBFAMILY SC WARNING ENTRY !!!! [H. sapiens ] RC_AA007158_f_at 4 AA007158 ESTs −2.0 0.001870921 RC_Z38785_at 1109 Z38785 Homo sapiens clone 23940 mRNA −2.0 0.013437083 sequence RC_AA282247_at 204 AA282247 ESTs −2.0 0.000515617 RC_T23935_s_at 887 T23935 ESTs, Weakly similar to protein- −2.0 0.006493804 tyrosine phosphatase [H. sapiens ] RC_R59593_at 848 R59593 ESTs −2.0 0.014592934 RC_AA446241_at 345 AA446241 tropomyosin 2 (beta)9p13.2-p13.1 −2.0 0.040680667 RC_Z40556_at 1116 Z40556 DJ222E13.1a.1 (C-terminal part of −2.0 0.019444878 novel protein dJ222E13.1) (partial isoform 1) RC_AA159025_at 100 AA159025 ESTs, Highly similar to (defline not −2.0 0.01375696 available 4680655) [H. sapiens ] RC_H03387_s_at 546 H03387 estrogen-responsive B box −2.0 0.036382844 protein17p11.2 RC_H17333_at 558 H17333 EST −2.0 0.018111182 RC_AA412722_s_at 289 AA412722 putative cyclin G1 interacting −2.0 0.006838915 protein7 U65579_at 979 U65579 NADH dehydrogenase (ubiquinone) −2.0 0.013707565 Fe-S protein 8 (23 kD) (NADH- coenzyme Q reductase)11q13 RC_R88209_at 860 R88209 ESTs −2.0 0.040272012 RC_Z38266_at 1106 Z38266 Homo sapiens PAC clone −2.0 0.009414008 DJ0777O23 from 7p14-p15

[0142] TABLE 2 Normal1-Normal2 vs BPH-Cancer (Up-regulated) Fold-Change p-value SEQ ID N1-N2 vs N1-N2 vs Affymetrix element NO: Genbank ID Genbank Name Cancer Cancer L49169_at 649 L49169 FBJ murine osteosarcoma viral oncogene 18.8 0.03580379 homolog B19c113.3 RC_N23730_s_at 724 N23730 v-fos FBJ murine osteosarcoma viral oncogene 16.5 8.98673E−05 homolog14q24.3 V01512_rnal_at 993 V01512 v-fos FBJ murine osteosarcoma viral oncogene 16.0 0.001216643 homolog14q24.3 RC_T90619_f_at 926 T90619 actin, gamma 117q25 15.7 0.044124187 U20734_s_at 952 U20734 jun B proto-oncogene19p13.2 14.3 0.004404553 U62015_at 978 U62015 insulin-like growth factor binding protein 101p22- 13.8 0.000487216 p31 AA374109_at 241 AA374109 ESTs, Moderately similar to (define not available 13.0 0.025911461 5031506) [R. norvegicus] RC_T79768_at 914 T79768 ESTs 12.2 0.018940142 RC_AA410383_at 277 AA410383 B-cell-homing chemokine (ligand for Burkitt's 11.1 0.046025784 lymphoma receptor-1)4q21 X52541_at 1064 X52541 early growth response 15q31.1 9.7 0.003167537 RC_N66802_at 767 N66802 early growth response 38p23-p21 9.7 0.026764792 RC_AA463726_s_at 386 AA463726 JM27 proteinXp11.23 9.4 0.003409168 N40141_at 743 N40141 JM27 proteinXp11.23 8.4 0.021768214 M34996_s_at 685 M34996 major histocompatibility complex, class II, DQ 7.7 0.015886207 alpha 16p21.3 RC_T67053_f_at 909 T67053 immumoglobulin lambda gene cluster22q11.1- 7.4 0.000196865 q11.2 RC_AA404957_at 266 AA404957 ESTs, Highly similar to MATRIX GLA-PROTEIN 6.6 0.011451385 PRECURSOR [H. sapiens] RC_H64493_f_at 590 H64493 immunoglobulin gamma 3 (Gm marker)14q32.33 6.5 0.002716347 RC_N47686_s_at 744 N47686 solute carrier family 14 (urea transporter), member 6.3 0.015568892 1 (Kidd blood group)18q11-q12 RC_W44760_s_at 1006 W44760 frizzled-related protein2qter 6.3 0.016891036 L19871_at 642 L19871 activating transcription factor 3 6.2 0.007603286 M92934_at 708 M92934 connective tissue growth factor6q23.1 6.1 0.001046931 M62831_at 695 M62831 immediate early protein19 5.8 0.00753286 L22524_s_at 643 L22524 matrix metalloproteinase 7 (matrilysin, 5.8 0.048289798 uterine)11q21-q22 J03507_at 621 J03507 complement component 75p13 5.6 0.00240657 RC_AA236455_r_at 153 AA236455 ESTs 5.5 0.022653542 RC_AA450127_at 359 AA450127 growth arrest and DNA-damage-inducible, 5.5 0.023227588 beta19p13.3 RC_AA281345_f_at 201 AA281345 immediate early protein19 5.4 0.003661068 RC_N30198_at 733 N30198 ESTs 5.3 0.005657756 AFFX- 1040 X00351 Human mRNA for beta-actin 5.3 0.01547291 HSAC07/X00351_5_at D83018_at 513 D83018 nel (chicken)-like 212q13.11-q13.12 5.1 0.003774757 J04111_at 624 J04111 Jun activation domain binding protein1p32-p31 5.0 0.000243067 X51345_at 1062 X51345 jun B proto-oncogene19p13.2 5.0 0.017173421 RC_AA398903_at 250 AA398903 ESTs, Weakly similar to !!!! ALU SUBFAMILY J 4.9 0.014577818 WARNING ENTRY !!!! [H. sapiens] RC_H17550_at 559 H17550 ESTs 4.7 0.012079391 S81914_at 873 S81914 immediate early response 36p21.3 4.5 0.006218653 RC_AA250958_f_at 167 AA250958 EST 4.4 1.88343E−05 L49169_at 649 L49169 FBJ murine osteosarcoma viral oncogene 18.8 0.03580379 homolog B19q13.3 RC_N23730_s_at 724 N23730 v-fos FBJ murine osteosarcoma viral oncogene 16.5 8.98673E−05 homolog14q24.3 RC_AA446651_at 346 AA446651 ESTs 4.4 0.026022802 HG1872-HT1907_at 674 M28590 Human (clone pcDG-79) MHC HLA-DG protein 41 4.3 0.008830524 mRNA, partial cds. RC_AA490667_at 419 AA490667 ESTs 4.3 0.048863016 RC_N67041_at 768 N67041 ESTs 4.1 0.009333688 V00563_at 991 V00563 immunoglobulin mu14q32.33 4.1 0.004301939 X57809_s_at 1069 X57809 immumoglobulin lambda gene cluster22q11.1- 4.1 0.025371658 q11.2 R69417_at 852 R69417 ESTs 4.1 0.046373179 J00231_f_at 617 J00231 immunoglobulin gamma 3 (Gm marker)14q32.33 4.0 0.004766015 RC_AA402903_f_at 263 AA402903 immunoglobulin gamma 3 (Gm marker)14q32.33 3.9 0.000172905 U21128_at 953 U21128 lumican12q21.3-q22 3.9 0.000708917 M12529_at 655 M12529 apolipoprotein E19q13.2 3.7 0.026856247 RC_AA436616_at 335 AA436616 ESTs 3.7 0.020860083 U72649_at 983 U72649 B-cell translocation gene 2 (pheochromacytoma 3.7 0.002487396 cell-3)1q32 X03689_s_at 1044 X03689 Human mRNA fragment for elongation factor TU 3.7 0.04821902 (N-terminus) AFFX- 1040 X00351 Human mRNA for beta-actin 3.6 0.029717275 HSAC07/X00351_5_at RC_T62857_at 903 T62857 ESTs 3.6 0.002846539 Z74616_s_at 1123 Z74616 collagen, type I, alpha 27q22.1 3.6 0.004328291 X06700_s_at 1049 X06700 collagen, type III, alpha 1 (Ehlers-Danlos 3.6 0.010596098 syndrome type IV, autosomal dominant)2q31 RC_H86112_f_at 600 H86112 KIAA0471 gene product1q24-q25 3.6 0.017013968 M57466_s_at 690 M57466 major histocompatibility complex, class II, DP beta 3.5 0.005924671 16p2l.3 RC_F09281_at 533 F09281 ESTs 3.5 0.006841731 RC_R51831_at 843 R51831 ESTs 3.4 0.000941423 RC_H21814_f_at 563 H21814 immumoglobulin lambda gene cluster22q11.1- 3.4 0.009767098 q11.2 RC_W86513_at 1033 W86513 ESTs 3.4 0.003776481 RC_H40424_s_at 572 H40424 EST 3.4 0.016283906 X57025_at 1066 X57025 insulin-like growth factor 1 (somatomedin C)12q22 3.3 0.040489253 q23 RC_AA044219_at 29 AA044219 BK984G1.1 (PUTATIVE C-terminal end of a novel 3.3 0.001761114 protein with Collagen triple helix repeats) RC_AA028092_s_at 17 AA028092 transcription factor 216pter-qter 3.3 0.003405482 RC_AA446661_at 347 AA446661 ESTs 3.3 0.041188995 RC_D80063_f_at 506 D80063 ESTs 3.3 0.049585142 M92843_s_at 707 M92843 zinc finger protein homologous to Zfp-36 in 3.3 0.006174082 mouse19q13.1 M34516_r_at 684 M34516 immunoglobulin lambda-like polypeptide 322q11.2 3.2 0.02344053 L49169_at 649 L49169 FBJ murine osteosarcoma viral oncogene 18.8 0.03580379 homolog B19q13.3 RC_N23730_s_at 724 N23730 v-fos FBJ murine osteosarcoma viral oncogene 16.5 8.98673E−05 homolog14q24.3 M87789_s_at 704 M87789 immunoglobulin gamma 3 (Gm marker)14q32.33 3.2 0.004534646 N75870_s_at 780 N75870 dual specificity phosphatase 15q34 3.2 0.000157434 RC_AA609309_at 442 AA609309 ESTs, Moderately similar to !!!! 3.1 0.03780658 ALU SUBFAMILY SB2 WARNING ENTRY !!!! [H. sapiens] S59049_at 870 S59049 regulator of G-protein signalling 11q31 3.0 0.002419303 AFFX- 679 M33197 Human GAPDH 3.0 0.034538288 HUMGAPDH/M33197_5_at RC_D51060_s_at 495 D51060 Jun activation domain binding protein1p32-p31 3.0 0.022390037 RC_T23468_at 884 T23468 ESTs 2.9 0.001634616 U30521_at 960 U30521 P311 protein 2.9 0.009484198 Z48501_s_at 1121 Z48501 poly(A)-binding protein-like 13q22-q25 2.9 0.026396977 W73859_at 1028 W73859 transcription factor 216pter-qter 2.9 0.037326183 AA093923_at 63 AA093923 tissue inhibitor of metalloproteinase 217q25 2.8 0.041564022 RC_AA236476_at 154 AA236476 ESTs, Weakly similar to (defline not available 2.7 0.038305276 4507549) [H. sapiens] U10550_at 944 U10550 GTP-binding protein overexpressed in skeletal 2.7 0.040657885 muscle8q13-q21 RC_N24902_at 727 N24902 E1B-55kDa-associated protein 5 2.7 0.03810507 RC_AA056121_at 46 AA056121 ESTs 2.7 0.024285705 RC_H98835_at 611 H98835 ESTs 2.7 0.019901442 K02405_f_at 629 K02405 Human MHC class II HLA-DQ-beta mRNA (DR7 2.7 0.00138806 DQw2), complete cds U90552_s_at 988 U90552 butyrophilin, subfamily 3, member A16p23 2.7 3.91186E−05 RC_N59831_at 759 N59831 ESTs 2.7 0.04543669 L33799_at 645 L33799 procollagen C-endopeptidase enhancer7q22 2.7 0.010879277 RC_N59532_s_at 758 N59532 aminomethyltransferase (glycine cleavage system 2.6 0.025712285 protein T)3p21.2-p21.1 D13628_at 476 D13628 angiopoietin 16q22.3-q23 2.6 0.027204836 AA156897_s_at 97 AA156897 Homo sapiens mRNA; cDNA DKFZp564I1922 2.6 0.001580022 (from clone DKFZp564I1922) RC_N67876_s_at 773 N67876 insulin-like growth factor 1 (somatomedin C)12q22 2.6 0.03992641 q23 M73720_at 702 M73720 carboxypeptidase A3 (mast cell)3q21-q25 2.6 0.023298997 H49440_at 578 H49440 nudix (nucleoside diphosphate linked moiety X)- 2.6 0.002498701 type motif 36p21.2 RC_AA250850_at 166 AA250850 adrenergic, beta, receptor kinase 222q11 2.5 0.041156086 RC_T49061_at 894 T49061 ESTs 2.5 0.00934004 W28214_at 996 W28214 ESTs 2.5 0.037677921 RC_H44631_s_at 573 H44631 immediate early protein19 2.5 0.0423037 D28137_at 484 D28137 bone marrow stromal cell antigen 219p13.2 2.5 0.026212334 RC_AA609027_at 441 AA609027 ESTs 2.5 0.038550623 RC_AA257093_r_at 178 AA257093 T-cell receptor, beta cluster7q35 2.4 0.002653232 RC_F13763_at 542 F13763 ESTs 2.4 0.016949277 RC_H08548_s_at 550 H08548 ATP citrate lyase17q12-q21 2.4 0.036998522 RC_AA436618_at 336 AA436618 ESTs 2.4 0.001789907 L49169_at 649 L49169 FBJ murine osteosarcoma viral oncogene 18.8 0.03580379 homolog B19q13.3 RC_N23730_s_at 724 N23730 v-fos FBJ murine osteosarcoma viral oncogene 16.5 8.98673E−05 homolog14q24.3 RC_W45664_s_at 1008 W456645 nucleotidase (CD73)6q14-q21 2.4 0.001762727 AA082546_at 54 AA082546 ESTs 2.4 0.021791878 D10522_at 471 010522 myristoylated alanine-rich protein kinase C 2.4 0.017333686 substrate (MARCKS, 80 K-L)6q22.2 RC_AA411860_at 280 AA411860 ESTs, Highly similar to (defline not available 2.4 0.02766922 4929723) [H. sapiens] AB002340_at 461 AB002340 KIAA0342 gene product 2.3 0.003238699 U53445_at 972 U53445 downregulated in ovarian cancer 13 2.3 0.009361652 AA091278_at 60 AA091278 ESTs 2.3 0.046253689 RC_AA486072_i_at 410 AA486072 small inducible cytokine A5 (RANTES)17q11.2- 2.3 0.012816473 q12 RC_T53590_s_at 899 T53590 cytochrome P450, subfamily XIA (cholesterol side 2.3 4.29636E−05 chain cleavage)15q23-q24 RC_N91971_f_at 791 N91971 retinol-binding protein 1, cellular3q23 2.3 0.025171598 RC_AA043777_at 28 AA043777 ESTs 2.3 0.004490188 RC_H54764_at 580 H54764 EST, Weakly similar to X-linked retinopathy 2.3 0.036980431 protein {C-terminal, clone XEH.8c} [H. sapiens] RC_AA443923_at 344 AA443923 ESTs 2.3 0.025833241 U60975_at 977 U60975 Homo sapiens gp250 precursor, mRNA, complete 2.3 0.041238204 cds. M34516_at 684 M34516 immunoglobulin lambda-like polypeptide 322q11.2 2.3 0.041388637 RC_N36001_at 740 N36001 ESTs, Weakly similar to !!!! ALU CLASS C 2.2 0.000449076 WARNING ENTRY !!!! [H. sapiens] AF010193_at 464 AF010193 MAD (mothers against decapentaplegic, 2.2 0.005397771 Drosophila) homolog 718 AFFX- 1040 X00351 Human mRNA for beta-actin 2.2 0.037852217 HSAC07/X00351_5_at RC_AA158262_s_at 99 AA158262 calpastatin5q14-q22 2.2 0.006648962 RC_AA156565_at 96 AA156565 4-nitrophenylphosphatase domain and non- 2.2 0.020901922 neuronal SNAP25-like 122q12 Z11793_at 1104 Z11793 selenoprotein P, plasma, 15q31 2.2 0.00118281 RC_D80059_s_at 504 D80059 ESTs 2.2 0.033534432 RC_AA450324_at 360 AA450324 ESTs 2.2 0.024832006 RC_N39415_at 742 N39415 osteoglycin (osteoinductive factor) 2.2 0.032001116 RC_T23622_at 886 T23622 ESTs 2.2 0.040417825 RC_AA599365_at 434 AA599365 decorin12q23 2.2 0.011325181 X62320_at 1073 X62320 granulin17 2.2 0.043043858 RC_R85291_at 859 R85291 ESTs 2.2 0.004987693 M11313_s_at 654 M11313 alpha-2-macroglobulin12p13.3-p12.3 2.2 0.011545737 AA047151_at 37 AA047151 ESTs 2.2 0.033987576 RC_AA205724_at 123 AA205724 ESTs 2.2 0.004569368 RC_AA086264_i_at 59 AA086264 ESTs, Highly similar to (defline not available 2.2 0.020637423 4191348) [H. sapiens] RC_R42424_at 832 R42424 ESTs 2.2 0.033603417 RC_AA347359_s_at 233 AA347359 lysozyme (renal amyloidosis)12 2.1 0.028764499 L49169_at 649 L49169 FBJ murine osteosarcoma viral oncogene 18.8 0.03580379 homolog B19q13.3 RC_N23730_s_at 724 N23730 v-fos FBJ murine osteosarcoma viral oncogene 16.5 8.98673E−05 homolog14q24.3 AA092716_at 62 AA092716 HLA-B associated transcript-36p21.3 2.1 0.031717351 RC_R42241_at 830 R42241 ESTs 2.1 0.008013968 RC_N57577_at 756 N57577 KIAA0663 gene product 2.1 0.032028875 RC_W67577_s_at 1022 W67577 CD74 antigen (invariant polypeptide of major 2.1 0.002072118 histocompatibility complex, class II antigen- associated)5q32 C02016_at 466 C02016 KIAA0447 gene product 2.1 0.002399894 RC_AA256268_at 175 AA256268 ESTs 2.1 0.0269568 RC_T96171_at 930 T96171 EST 2.1 0.012219229 X72841_at 1083 X72841 retinoblastoma-binding protein 7 2.1 0.033774692 RC_R45698_at 839 R45698 ESTs 2.1 0.049975895 RC_N22006_s_at 719 N22006 EST 2.1 0.011131338 RC_N69222_at 777 N69222 ESTs 2.1 0.022256915 RC_H97538_at 607 H97538 ESTs 2.0 0.03795259 RC_AA039935_at 23 AA039935 dynein light chain, outer arm 422q12.3-q13.2 2.0 0.011488766 RC_AA084138_at 55 AA084138 ESTs 2.0 0.011124432 AB002379_at 462 AB002379 KIAA0381 protein 2.0 0.000530413 RC_AA460651_at 379 AA460651 heterogeneous nuclear protein similar to rat helix 2.0 0.027697892 destabilizing protein10 RC_W02204_at 994 W02204 solute carrier family 24 2.0 0.00115779 (sodium/potassium/calcium exchanger), member 115q22 Y08614_at 1101 Y08614 exportin 1 (CRM1, yeast, homolog)2p16 2.0 0.035368368 D31134_at 488 D31134 KIAA1075 protein 2.0 0.021196526 M94880_f_at 711 M94880 major histocompatibility complex, class I, A6p21.3 2.0 0.025382167 J03040_at 619 J03040 secreted protein, acidic, cysteine-rich 2.0 0.035472553 (osteonectin)5q31.3-q32 RC_N68350_at 775 N68350 ESTs 2.0 0.042917893 RC_H48793_at 577 H48793 EST 2.0 0.00296551 HG3543-HT3739_at 675 M29645 insulin-like growth factor 2 (somatomedin 2.0 0.019712374 A)11p15.5 RC_W33172_at 999 W33172 ESTs, Weakly similar to ORF2 [M. musculus] 2.0 0.006454106 RC_R08850_at 806 R08850 ESTs 2.0 0.011364766 W52638_at 1014 W52638 ESTs 2.0 0.010612401 M19045_f_at 662 M19045 lysozyme (renal amyloidosis)12 2.0 0.004561974 RC_AA312946_s_at 228 AA312946 ESTs 2.0 0.020272205 RC_AA235310_at 148 AA235310 ESTs 2.0 0.011954937 X03100_cds2_at 1043 X03100 Human mRNA for SB classII histocompatibility 2.0 0.002404541 antigen alpha-chain RC_T16282_f_at 881 T16282 wee1 + (S. pombe)homolog11p15.3-p15.1 2.0 0.031472155 RC_H66642_f_at 591 H66642 ESTs, Moderately similar to !!!! 2.0 0.02460529 ALU SUBFAMILY SQ WARNING ENTRY !!!! [H. sapiens] RC_AA342337_at 231 AA342337 ESTs, Moderately similar to !!!! −23.7 3.26344E−05 ALU SUBFAMILY SQ WARNING ENTRY !!!! [H. sapiens] L49169_at 649 L49169 FBJ murine osteosarcoma viral oncogene 18.8 0.03580379 homolog B19q13.3 RC_N23730_s_at 724 N23730 v-fos FBJ murine osteosarcoma viral oncogene 16.5 8.98673E−05 homolog14q24.3 RC_AA398908_at 251 AA398908 Human Chromosome 16 BAC clone CIT987SK-A- −21.7 0.040053626 61E3 RC_H15143_s_at 554 H15143 Human clone 23575 mRNA, partial cds −13.8 0.028261625 RC_N80129_i_at 785 N80129 metallothionein 1L16q13 −12.6 0.002146038 RC_AA465394_at 390 AA465394 ESTs −12.6 0.004961162 RC_AA236545_at 156 AA236545 ESTs −12.5 0.034938167 RC_W42778_at 1004 W42778 Homo sapiens clone 24636 mRNA sequence −12.3 0.010449419 RC_T40895_at 892 T40895 ESTs −12.0 0.01968535 RC_H94475_s_at 605 H94475 alpha-2-plasmin inhibitor17pter-p12 −11.7 0.012919819 RC_R71792_s_at 855 R71792 ESTs, Moderately similar to FAT-SPECIFIC −10.4 0.002540356 PROTEIN FSP27 [M. musculus] RC_AA609006_at 440 AA609006 ESTs −7.5 0.013902978 RC_AA026641_s_at 16 AA026641 secretory leukocyte protease inhibitor −7.0 0.01850877 (antileukoproteinase) X65614_at 1076 X65614 S100 calcium-binding protein P4p16 −6.7 0.005634308 X93036_at 1093 X93036 phospholemman-like, expressed in breast tumors, −6.6 0.005278275 8 kD RC_T94447_s_at 928 T94447 ESTs, Moderately similar to (defline not available −5.7 0.006891909 4335935) [M. musculus] RC_AA405488_at 268 AA405488 ESTs −5.5 0.00023986 RC_T73433_s_at 912 T73433 angiotensinogen1q41-qter −5.5 0.009418205 M99487_at 716 M99487 folate hydrolase (prostate-specific membrane −5.3 0.008067789 antigen) 111p11.2 RC_W88568_at 1035 W88568 glycogenin 2Xp22.3 −5.1 0.024739084 RC_AA460914_at 380 AA460914 ESTs −5.0 0.024385552 X57129_at 1067 X57129 H1 histone family, member 26p21.3 −4.8 0.006322499 RC_Z41642_at 1119 Z41642 ESTs −4.7 0.009525521 RC_R46074_at 840 R46074 transforming, acidic coiled-coil containing protein −4.7 0.001327844 210q26 J03910_rna1_at 622 J03910 metallothionein 1G16q13 −4.6 0.004574277 RC_AA350265_at 237 AA350265 histone deacetylase A −4.5 0.002897414 AA165312_at 103 AA165312 ESTs −4.2 0.005487803 RC_AA419011_at 296 AA419011 Homo sapiens mRNA; cDNA DKFZp586D0823 −4.0 0.019079557 (from clone DKFZp58600823) RC_N92502_s_at 794 N92502 ESTs, Moderately similar to HERV-E integrase −4.0 0.030144039 [H. sapiens] RC_F03969_at 528 F03969 ESTs, Weakly similar to tumorous imaginal discs −4.0 0.017024613 protein Tid56 homolog [H. sapiens] X76717_at 1087 X76717 metallothionein 1L16q13 −3.9 0.001145402 RC_AA416762_s_at 291 AA416762 nuclear receptor subfamily 1, group H, member −3.8 0.011735303 219q13.3-19q13.3 RC_AA053424_at 40 AA053424 ESTs, Weakly similar to mucin Muc3 −3.8 0.009737433 [R. norvegicus] X64177_f_at 1075 X64177 metallothionein 1H16q13 −3.7 0.003297195 RC_N32748_at 736 N32748 ESTs −3.6 0.021454174 RC_AA416685_at 290 AA416685 UNC13 (C. elegans)-like9p11-p12 −3.6 0.016338392 RC_AA505136_at 426 AA505136 ESTs −3.5 0.007200396 RC_AA165313_at 104 AA165313 ESTs −3.5 0.037649191 L49169_at 649 L49169 FBJ murine osteosarcoma viral oncogene 18.8 0.03580379 homolog B19q13.3 RC_N23730_s_at 724 N23730 v-fos FBJ murine osteosarcoma viral oncogene 16.5 8.98673E−05 homolog14q24.3 RCF02245_at 522 F02245 monoamine oxidase AXp11.4-p11.3 −3.4 0.005486135 RC_AA004699_at 1 AA004699 putative translation initiation factor −3.4 0.00057505 RC_AA599331_at 433 AA599331 ESTs −3.4 0.01136457 RC_N26904_at 731 N26904 ESTs, Weakly similar to FK506/rapamycin-binding −3.3 0.045410608 protein FKBP13 precursor [H. sapiens] RC_AA070752_s_at 51 AA070752 insulin receptor substrate 12q36 −3.3 0.028433761 RC_AA599522_f_at 437 AA599522 squamous cell carcinoma antigen recognised by −3.2 0.005311305 T cells RC_N94303_at 797 N94303 ESTs −3.1 0.000160723 RC_F10078_at 538 F10078 ESTs −3.1 0.022464594 RC_AA447537_at 350 AA447537 ESTs, Moderately similar to (defline not available −3.1 0.007323728 5360237) [M. musculus] L77701_at 651 L77701 human homolog of yeast mitochondrial copper −3.0 0.001489928 recruitment gene RC_H27675_at 569 H27675 ESTs −3.0 0.016160504 V00594_at 992 V00594 metallothionein 2A16q13 −2.9 0.001495259 U52969_at 970 U52969 Purkinje cell protein 421q22.2-q22.3 −2.9 6.3447E−05 RC_R42607_at 834 R42607 ESTs −2.8 0.008960052 RC_AA451836_at 362 AA451836 ESTs −2.7 0.008401586 RC_F04492_at 531 F04492 ESTs, Weakly similar to !!!! ALU SUBFAMILY J −2.7 0.001443051 WARNING ENTRY !!!! [H. sapiens] RC_H77597_f_at 594 H77597 metallothionein 1H16q13 −2.7 0.00332868 RC_AA430388_at 321 AA430388 ESTs, Moderately similar to !!!! −2.7 0.000114004 ALU SUBFAMILY SQ WARNING ENTRY !!!! [H. sapiens] RC_T90190_s_at 925 T90190 H1 histone family, member 26p21.3 −2.7 0.030242714 RC_H16171_f_at 555 H16171 cleft lip and palate associated transmembrane −2.7 0.023414443 protein 119q13.2-q13.3 RC_AA022886_at 14 AA022886 ESTs, Weakly similar to phosphatidylinositol −2.7 0.00489294 transfer protein [H. sapiens] RC_R28370_at 815 R28370 ESTs −2.7 0.003724547 RC_AA261907_at 182 AA261907 ESTs, Weakly similar to (define not available −2.6 0.043689441 3874144) [C. elegans] RC_W37778_f_at 1002 W37778 ESTs, Weakly similar to envelope protein −2.6 0.030756837 [H. sapiens] RC_T98019_at 932 T98019 EST, Highly similar to PEREGRIN [H. sapiens] −2.5 0.035566681 RC_N33927_s_at 737 N33927 H2B histone family, member B6p21.3 −2.5 0.013093926 RC_R40431_at 828 R40431 Homo sapiens mRNA; cDNA DKFZp564D016 −2.5 0.004235538 (from clone DKFZp564D016) RC_AA133756_at 78 AA133756 Rho-associated, coiled-coil containing protein −2.5 0.012389163 kinase 22p24 RC_AA152200_s_at 92 AA152200 ESTs −2.5 0.004366137 W63793_at 1020 W63793 S-adenosylmethionine decarboxylase 16q21-q22 −2.5 0.005714247 RC_AA410298_at 274 AA410298 ESTs −2.5 0.018744617 X99728_at 1098 X99728 H. sapiens NDUFV3 gene, exon 3 −2.5 0.004580383 RC_W78127_at 1031 W78127 ESTs, Weakly similar to KIAA0425 [H. sapiens] −2.5 0.001240164 L49169_at 649 L49169 FBJ murine osteosarcoma viral oncogene 18.8 0.03580379 homolog 819q13.3 RC_N23730_s_at 724 N23730 v-fos FBJ murine osteosarcoma viral oncogene 16.5 8.98673E−05 homolog14q24.3 RC_R96924_a_at 866 R96924 ESTs −2.5 0.006515911 RC_H16768_at 557 H16768 ESTs −2.5 0.005669237 X76180_at 1086 X76180 sodium channel, nonvoltage-gated 1 alpha12p13 −2.5 0.007625025 RC_AA432162_at 324 AA432162 Homo sapiens mRNA; cDNA DKFZp58682022 −2.4 0.010199113 (from clone DKFZp586B2022) RC_H88798_at 602 H88798 ESTs −2.4 0.000783143 RC_AA609312_at 443 AA609312 ESTs −2.4 0.016243321 RC_AA131919_at 75 AA131919 putative type II membrane protein −2.4 0.000264791 RC_N80129_f_at 785 N80129 metallothionein 1L16q13 −2.4 0.002297016 RC_AA182030_at 110 AA182030 ESTs −2.4 0.041632378 W70167_at 1025 W70167 ESTs −2.4 0.00395969 RC_AA599522_r_at 437 AA599522 squamous cell carcinoma antigen recognised by T −2.4 0.004347078 cells RC_N52254_s_at 749 N52254 SH3-binding domain glutamic acid-rich −2.4 0.011171389 protein21q22.3 RC_N95495_at 799 N95495 small inducible cytokine A5 (RANTES)17q11.2- −2.4 0.002430242 q12 RC_T68873_f_at 911 T68873 metallothionein 1L16q13 −2.4 0.00320019 AA429539_f_at 318 AA429539 ESTs −2.4 0.020751882 RC_AA435769_s_at 330 AA435769 ESTs −2.4 0.009832353 RC_AA029356_at 18 AA029356 ESTs −2.3 0.007208722 AA316686_s_at 229 AA316686 ESTs, Highly similar to huntingtin interacting −2.3 0.000225753 protein HYPK [H. sapiens] RC_H02308_at 545 H02308 ESTs −2.3 0.041776289 RC_AA258476_at 179 AA258476 Homo sapiens mRNA; cDNA DKFZp564J0323 −2.3 0.02070961 (from clone DKFZp564J0323) X06956_at 1051 X06956 tubulin, alpha 1 (testis specific)2q −2.3 0.003656874 RC_H99694_at 614 H99694 ESTs −2.3 0.013645335 RC_AA479044_s_at 402 AA479044 ESTs, Weakly similar to PROGASTRICSIN −2.3 0.047032301 PRECURSOR [H. sapiens] RC_AA436861_at 340 AA436861 ESTs −2.3 0.001794201 M24069_at 672 M24069 cold shock domain protein A12p13.1 −2.3 0.014123514 RC_AA410311_at 275 AA410311 ESTs −2.3 0.045227011 W52858_at 1015 W52858 Homo sapiens mRNA; cDNA DKFZp564F0522 −2.3 0.002276405 (from clone DKFZp564F0522) RC_W38197_at W38197 EST −2.3 1.96016E−05 J00073_at 615 J00073 actin, alpha, cardiac muscle15q11-qter −2.3 0.018476889 RC_D51069_f_at 496 D51069 melanoma adhesion molecule −2.3 0.042693395 RC_AA504805_s_at 424 AA504805 interferon stimulated gene (20 kD)15q26 −2.3 0.008805886 RC_F03254_f_at 527 F03254 synuclein, alpha (non A4 component of amyloid −2.3 0.003668915 precursor)4q21 M35252_at 686 M35252 tranamembrane 4 superfamily member 3 −2.3 0.028083185 RC_AA040731_at 25 AA040731 ESTs −2.2 0.028924808 RC_AA496247_at 422 AA496247 ESTs −2.2 0.013336314 X59766_at 1071 X59766 alpha-2-glycoprotein 1, zinc 7 −2.2 0.002003511 L49169_at 649 L49169 FBJ murine osteosarcoma viral oncogene 18.8 0.03580379 homolog B19q13.3 RC_N23730_s_at 724 N23730 v-fos FBJ murine osteosarcoma viral oncogene 16.5 8.98673E−05 homolog14q24.3 RC_R84421_at 857 R84421 eukaryotic translation elongation factor 1 alpha −2.2 0.016333706 16q14 AA328993_s_at 230 AA328993 ESTs −2.2 0.004438605 RC_R44535_f_at 836 R44535 endonuclease G9q34.1 −2.2 0.014319616 U41518_at 964 U41518 aquaporin 1 (channel-forming integral protein, −2.2 0.009447457 28 kD)7p14 RC_W33179_at 1000 W33179 testis-specific kinase 21p32 −2.2 0.001104272 RC_H58873_s_at 583 H58873 solute carrier family 2 (facilitated glucose −2.2 0.000238641 transporter), member 11p35-p31.3 RC_R31679_s_at 816 R31679 ESTs −2.2 0.01000414 RC_AA189083_at 114 AA189083 ESTs, Highly similar to (defline not available −2.2 0.002468046 4589468) [M. musculus] RC_AA251769_at 168 AA251769 ESTs, Weakly similar to Containing ATP/GTP- −2.2 0.010819016 binding site motif A(P-loop): Similar to C. elegans protein(P1:CEC47E128); Similar to Mouse alpha- mannosidase(P1:B54407) [H. sapiens] RC_W70131_at 1024 W70131 ESTs −2.2 0.02955725 RC_R09379_at 807 R09379 solute carrier family 11 (proton-coupled divalent −2.2 0.009730513 metal ion transporters), member 212q13 RC_AA621695_at 458 AA621695 ESTs −2.1 0.001994051 RC_H18947_at 561 H18947 ESTs −2.1 0.027246274 RC_AA219552_s_at 134 AA219552 ESTs −2.1 0.046510941 RC_N22620_at 722 N22620 ESTs −2.1 0.013527392 RC_R02003_r_at 804 R02003 ESTs, Weakly similar to cappuccino −2.1 0.010597095 [D. melanogaster] RC_AA405559_at 270 AA405559 ESTs −2.1 0.009305601 RC_AA463693_at 385 AA463693 ESTs, Weakly similar to SERINE/THREONINE- −2.1 0.004156996 PROTEIN KINASE NEK3 [H. sapiens] RC_AA481407_at 405 AA481407 ESTs −2.1 0.002741696 M11119_at 653 M11119 Human endogenous retrovirus envelope region −2.1 0.003718876 mRNA (PL1) RC_AA159025_at 100 AA159025 ESTs, Highly similar to (defline not available −2.1 0.011127532 4680655) [H. sapiens] RC_AA411981_at 283 AA411981 ESTs, Weakly similar to putative seven pass −2.1 0.044294612 transmembrane protein [H. sapiens] RC_W57931_at 1017 W57931 ESTs, Moderately similar to CATHEPSIN D −2.1 0.000755739 PRECURSOR [H. sapiens] X66899_at 1081 X66899 Ewing sarcoma breakpoint region 122q12 −2.1 0.002068901 RC_R49327_at 842 R49327 solute carrier family 11 (proton-coupled divalent −2.1 0.030928835 metal ion transporters), member 212q13 RC_AA609645_at 445 AA609645 eukaryotic translation initiation factor 4 gamma, −2.1 0.04955957 13q27-qter RC_AA434108_at 327 AA434108 Homo sapiens heat shock protein hsp40-3 mRNA, −2.1 0.034468752 complete cds X17567_s_at 1061 X17567 small nuclear ribonucleoprotein polypeptides B −2.1 0.014475221 and B120 L49169_at 649 L49169 FBJ murine osteosarcoma viral oncogene 18.8 0.03580379 homolog B19q13.3 RC_N23730_s_at 724 N23730 v-fos FBJ murine osteosarcoma viral oncogene 16.5 8.98673E−05 homolog 14q24.3 J04164_at 626 J04164 interferon-induced protein 17 −2.1 0.023410352 RC_AA135929_s_at 80 AA135929 ESTs, Highly similar to (defline not available −2.1 0.003009065 4103057) [M. musculus] L04270_at 634 L04270 lymphotoxin beta receptor (TNFR superfamily, −2.1 0.006776988 member 312p13 RC_H99035_at 612 H99035 ESTs −2.1 0.001053584 M64673_at 698 M64673 heat shock transcription factor 1 −2.1 0.004283001 X85785_rna1_at 1091 X85785 Duffy blood group1q21-q22 −2.1 0.00657464 M68864_at 700 M68864 Human ORF mRNA, complete cds −2.1 0.010185833 D50928_at 494 D50928 KIAA0138 gene product −2.1 0.002283064 RC_AA282247_at 204 AA282247 ESTs −2.0 0.007970044 RC_R00144_at 801 R00144 ESTs −2.0 0.006939854 RC_AA485965_at 409 AA485965 ESTs, Highly similar to (defline not available −2.0 0.000405037 4336766) [H. sapiens] S45630_at 869 S45630 crystallin, alpha B11q22.3-q23.1 −2.0 0.006157273 RC_T89703_at 923 T89703 ESTs, Highly similar to (defline not available −2.0 0.000286616 4455129) [H. sapiens] RC_Z38785_at 1109 Z38785 Homo sapiens clone 23940 mRNA sequence −2.0 0.00706437 X85373_at 1090 X85373 small nuclear ribonucleoprotein polypeptide G −2.0 6.93881E−05 RC_F04816_at 532 F04816 ESTs −2.0 0.005353184 RC_AA043349_at 27 AA043349 ESTs −2.0 0.01749596 RC_H84761_s_at 599 H84761 glutathione peroxidase 13p21.3 −2.0 0.000116621 M34338_s_at 683 M34338 spermidine synthase1p36-p22 −2.0 0.008566137 L13698_at 638 L13698 growth arrest-specific 19q21.3-q22.1 −2.0 0.016504513 RC_N75960_at 781 N75960 ESTs −2.0 0.024082428 D45370_at 491 D45370 adipose specific 210 −2.0 0.034362163 RC_AA401965_at 258 AA401965 tumor suppressor deleted in oral cancer-related −2.0 0.011190087 111q13 RC_F09315_at 534 F09315 discs, large (Drosophila) homolog 510q23 −2.0 0.020753036 RC_AA025370_at 15 AA025370 KIAA0872 protein −2.0 0.026565555 RC_H52835_at 579 H52835 phytanoyl-CoA hydroxylase (Refsum −2.0 0.015021251 disease)10pter-p11.2 RC_H99648_s_at 613 H99648 DNA segment, single copy probe LNS-CAI/LNS- −2.0 0.012115852 CAII (deleted in polyposis5q22-q23 RC_AA430074_at 320 AA430074 ESTs −2.0 0.002355049 RC_AA598939_at 428 AA598939 ESTs −2.0 0.011383872 AA455001_s_at 368 AA455001 ESTs −2.0 0.000176199 RC_F09684_at 535 F09684 ESTs −2.0 0.002741682 D42073_at 490 D42073 reticulocalbin 1, EF-hand calcium binding −2.0 0.012881688 domain11p13 RC_AA598695_at 427 AA598695 ESTs, Weakly similar to !!!! −2.0 4.77268E−06 ALU SUBFAMILY SX WARNING ENTRY !!!! [H. sapiens] D23662_at 481 D23662 neural precursor cell expressed, developmentally −2.0 0.003156141 down-regulated 8 RC_AA431470_at 323 AA431470 proteinkinase (cAMP-dependent, catalytic) −2.0 0.038692982 inhibitor gamma20q RC_AA399273_at 253 AA399273 ESTs −2.0 0.029403118 RC_AA142858_at 82 AA142858 ESTs −2.0 0.00197166 L49169_at 649 L49169 FBJ murine osteosarcoma viral oncogene 18.8 0.03580379 homolog B19q13.3 RC_N23730_s_at 724 N23730 v-fos FBJ murine osteosarcoma viral oncogene 16.5 8.98673E−05 homolog B4q24.3 RC_Z40715_at 1117 Z40715 Homo sapiens mRNA; cDNA DKFZp586C201 −2.0 0.017206338 (from clone DKFZp586C201) RC_AA490341_s_at 417 AA490341 ESTs −2.0 0.004570941 RC_N67815_f_at 772 N67815 ESTs, Weakly similar to (defline not available −2.0 0.002996692 4660655) [H. sapiens] RC_N53359_at 750 N53359 ESTs −2.0 0.034916164

[0143] TABLE 3 Normal vs. BPH W/Symptoms (Up-regulated) SEQ ID Fold- Affymetrix element NO: GenBank ID GenBank Name change t N40141_at 743 N40141 JM27 protein 17.4 −7.64 rc_N23730_s_at 724 N23730 v-fos FBJ murine osteosarcoma viral oncogene 10.8 −7.54 homolog rc_AA463726_s_at 386 AA463726 JM27 protein 10.0 −6.56 rc_N23352_s_at 723 N23352 proenkephalin 10.0 −4.53 rc_H64493_f_at 590 H64493 immunoglobulin heavy constant gamma 3 (G3m 9.1 −4.36 marker) V01512_rna1_at 993 V01512 v-fos FBJ murine osteosarcoma viral oncogene 9.1 −7.40 homolog rc_H05704_r_at 549 H05704 HCR (a-helix coiled-coil rod homologue) 8.1 −2.79 L49169_at 649 L49169 FBJ murine osteosarcoma viral oncogene 8.0 −5.81 homolog B rc_AA410383_at 277 AA410383 B-cell-homing chemokine (ligand for Burkitt's 7.5 −3.95 lymphoma receptor-1) rc_AA131322_s_at 74 AA131322 tryptase, alpha,tryptase, beta (tryptase II) 7.2 −2.81 R56183_s_at 844 R56183 eukaryotic translation initiation factor 3, subunit 6 6.9 −2.77 (48 kD) rc_AA461300_at 381 AA461300 ESTs 6.9 −7.08 J00231_f_at 617 J00231 immunoglobulin heavy constant gamma 3 (G3m 6.7 −4.62 marker) rc_AA427622_s_at 311 AA427622 collagen, type XIII, alpha 1 6.6 −8.25 rc_T90889_at 927 T90889 ESTs 5.6 −3.72 rc_AA402903_f_at 263 AA402903 immunoglobulin heavy constant gamma 3 (G3m 5.6 −3.61 marker) rc_T23622_at 886 T23622 ESTs 5.5 −5.24 rc_T62857_at 903 T62857 ESTs 5.4 −7.85 rc_AA256268_at 175 AA256268 ESTs 5.3 −6.86 rc_R44714_s_at 837 R44714 ESTs 5.3 −4.83 rc_AA236476_at 154 AA236476 transmembrane protein TENB2, 5.1 −3.13 rc_AA028092_s_at 17 AA028092 transcription factor 21 5.1 −5.24 rc_T90619_f_at 926 T90619 actin, gamma 1 5.0 −2.19 J00123_at 616 J00123 proenkephalin 5.0 −3.96 X52541_at 1064 X52541 early growth response 1 4.9 −5.78 rc_AA620825_at 454 AA620825 CGI-43 protein 4.9 −4.59 rc_AA424530_s_at 304 AA424530 ESTs 4.9 −5.42 rc_AA386386_s_at 246 AA386386 procollagen-proline, 2-oxoglutarate 4- 4.9 −2.64 dioxygenase (proline 4-hydroxylase), beta polypeptide (protein disulfide isomerase; thyroid hormone binding protein p55) U62015_at 978 U62015 cysteine-rich, angiogenic inducer, 61 4.9 −6.24 rc_AA188981_at 112 AA188981 highly expressed in cancer, rich in leucine 4.9 −6.67 heptad repeats rc_H21814_f_at 563 H21814 immunoglobulin lambda locus 4.9 −2.67 M60314_at 692 M60314 bone morphogenetic protein 5 4.7 −10.82 rc_T67053_f_at 909 T67053 immunoglobulin lambda locus 4.7 −2.84 rc_N47686_s_at 744 N47686 solute carrier family 14 (urea transporter), 4.7 −3.27 member 1 (Kidd blood group) rc_AA436616_at 335 AA436616 ESTs 4.7 −6.34 rc_H60595_s_at 585 H60595 progesterone binding protein 4.7 −2.66 rc_H88338_at 601 H88338 ESTs 4.7 −7.93 M33653_at 682 M33653 collagen, type XIII, alpha 1 4.6 −8.95 rc_N30198_at 733 N30198 ESTs 4.5 −5.87 D83018_at 513 D83018 nel (chicken)-like 2 4.5 −9.79 rc_Z39904_at 1111 Z39904 ESTs 4.5 −6.27 H61295_s_at 586 H61295 CD4 antigen (p55) 4.4 −4.49 rc_AA281345_f_at 201 AA281345 immediate early protein 4.3 −6.62 rc_T23490_s_at 885 T23490 hypothetical protein FLJ20185 4.2 −5.25 rc_AA279760_at 193 AA279760 DKFZP564M182 protein 4.2 −3.73 rc_R25410_at 814 R25410 ESTs 4.2 −4.69 rc_T03229_f_at 874 T03229 ESTs 4.2 −3.37 rc_R93908_at 865 R93908 ESTs 4.2 −3.39 AA374109_at 241 AA374109 spondin 2, extracellular matrix protein 4.2 −1.97 rc_R45654_at 838 R45654 collagen, type XIII, alpha 1 4.2 −5.69 rc_H86112_f_at 600 H86112 KIAA0471 gene product 4.1 −4.00 rc_AA257093_r_at 178 AA257093 T cell receptor beta locus 4.1 −7.77 rc_AA456147_at 371 AA456147 general transcription factor IIIA 4.1 −6.23 U21128_at 953 U21128 lumican 4.1 −6.15 rc_AA057195_at 47 AA057195 TNF? elastin microfibril interface located protein 4.1 −2.22 M63438_s_at 696 M63438 immunoglobulin kappa variable 1D-8 4.0 −2.53 M57466_s_at 690 M57466 major histocompatibility complex, class II, DP 4.0 −3.91 beta 1 rc_AA443923_at 344 AA443923 cat eye syndrome critical region gene 1 4.0 −3.01 rc_N39415_at 742 N39415 DKFZP586P2421 protein 4.0 −5.70 rc_W67225_at 1021 W67225 KIAA0592 protein 4.0 −3.35 M62831_at 695 M62831 immediate early protein 4.0 −6.39 rc_AA404957_at 266 AA404957 matrix Gla protein 4.0 −3.84 rc_F02992_at 526 F02992 ESTs 4.0 −3.65 U69263_at 982 U69263 matrilin 2 3.9 −4.84 rc_AA448625_at 354 AA448625 slit (Drosophila) homolog 3 3.9 −4.13 X57025_at 1066 X57025 insulin-like growth factor 1 (somatomedin C) 3.9 −3.93 AA151544_at 91 AA151544 matrix metalloproteinase 23B 3.8 −5.54 rc_F13763_at 542 F13763 ESTs 3.8 −6.39 rc_AA436655_at 337 AA436655 hypothetical protein FLJ10781 3.8 −5.13 M87789_s_at 704 M87789 immunoglobulin heavy constant gamma 3 (G3m 3.8 −3.93 marker) L44416_at 647 L44416 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3.8 −1.75 17 (72 kD) U20350_at 951 U20350 chemokine (C-X3-C) receptor 1 3.8 −6.50 rc_AA449749_at 355 AA449749 ESTs 3.8 −4.52 rc W73790_f_at 1027 W73790 immunoglobulin lambda-like polypeptide 1 3.7 −2.95 rc_AA281145_at 200 AA281145 ESTs 3.7 −1.77 rc_F09748_s_at 536 F09748 ESTs 3.7 −4.12 rc_T64211_at 906 T64211 HNOEL-iso protein 3.7 −5.35 rc_N80152_at 786 N80152 RNA binding motif protein 6 3.7 −2.40 rc_AA436618_at 336 AA436618 microtubule-associated protein 2 3.7 −4.67 T85532_f_at 917 T85532 ESTs 3.7 −1.90 rc_AA398280_at 248 AA398280 ESTs 3.6 −3.11 rc_T23468_at 884 T23468 CGI-119 protein 3.6 −4.67 AA195678_at 117 AA195678 actin binding protein; macrophin (microfilament 3.6 −3.48 and actin filament cross-linker protein) AB002335_at 460 AB002335 KIAA0337 gene product 3.6 −4.21 rc_AA598982_s_at 429 AA598982 KIAA1114 protein trophinin 3.6 −4.58 J03507_at 621 J03507 complement component 7 3.6 −6.21 J04130_s_at 625 J04130 small inducible cytokine A4 (homologous to 3.5 −4.76 mouse Mip-1b) AA495865_at 421 AA495865 ESTs 3.5 −3.65 HG3543-HT3739_at HG3543- insulin-like growth factor 2 (somatomedin A) 3.5 −4.69 HT3739 rc_AA599662_s_at 439 AA599662 KIAA0534 protein 3.5 −4.32 rc_AA486072_i_at 410 AA486072 small inducible cytokine A5 (RANTES) 3.5 −3.88 rc_Z39983_s_at 1112 Z39983 KIAA0561 protein 3.5 −5.56 rc_F02333_at 523 F02333 hypothetical protein FLJ20093 3.5 −2.23 rc_AA151210_at 89 AA151210 ESTs 3.5 −4.20 rc_N92239_at 793 N92239 Wnt inhibitory factor-1 3.5 −3.06 rc_AA173223_at 108 AA173223 ESTs 3.5 −5.22 rc_T86148_s_at 919 T86148 pituitary tumor-transforming 1 interacting protein 3.5 −2.15 AA214688_at 129 AA214688 eukaryotic translation initiation factor 4B 3.5 −3.13 rc_AA216589_at 131 AA216589 ESTs 3.5 −4.40 rc_AA446661_at 347 AA446661 hypothetical protein FLJ10970 3.4 −3.69 AA082546_at 54 AA082546 ESTs 3.4 −4.12 rc_W46395_at 1009 W46395 chromobox homolog 6 3.4 −2.41 rc_AA401433_at 257 AA401433 ESTs 3.4 −3.17 D62965_at 502 D62965 ESTs 3.4 −2.07 rc_AA057829_s_at 48 AA057829 growth arrest-specific 6 3.4 −2.00 rc_AA009755_at 6 AA009755 ESTs 3.3 −4.77 AA247204_at 163 AA247204 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3.3 −2.85 16 D13628_at 476 D13628 angiopoietin 1 3.3 −4.86 rc_N59866_at 761 N59866 ESTs 3.3 −4.39 rc_AA406371_at 273 AA406371 ESTs 3.3 −4.98 rc_N67876_s_at 773 N67876 insulin-like growth factor 1 (somatomedin C) 3.3 −3.06 M84526_at 703 M84526 D component of complement (adipsin) 3.3 −3.06 rc_AA234095_at 144 AA234095 hypothetical protein FLJ20701 3.3 −3.78 rc_D60074_s_at 498 D60074 cadherin 10 (T2-cadherin) 3.3 −5.05 rc_T49602_s_at 896 T49602 ESTs 3.3 −3.36 rc_n22006_s_at 718 N22006 ESTs 3.3 −3.88 rc_F04112_f_at 530 F04112 ESTs 3.3 −3.26 rc_T64223_s_at 907 T64223 carboxypeptidase A3 (mast cell) 3.3 −2.97 U23946_at 955 U23946 RNA binding motif protein 5 3.2 −3.48 rc_AA358038_at 238 AA358038 SH3-binding domain glutamic add-rich protein 3.2 −3.21 like rc_AA019433_at 12 AA019433 ESTs 3.2 −3.88 X03689_s_at 1044 X03689 eukaryotic translation elongation factor 1 alpha 1 3.2 −1.91 rc_H17550_at 559 H17550 ESTs 3.2 −2.90 rc_AA047880_at 38 AA047880 prothymosin, alpha (gene sequence 28) 3.2 −5.88 rc_AA084138_at 55 AA084138 ESTs 3.2 −7.93 rc_AA599365_at 434 AA599365 decorin 3.2 −4.42 rc_N91971_f_at 791 N91971 retinol-binding protein 1, cellular 3.2 −4.13 rc_T62873_at 904 T62873 ESTs 3.2 −2.12 rc_N49899_at 746 N49899 ESTs 3.2 −3.73 AA298981_at 226 AA298981 fibulin 5 3.2 −6.06 rc_AA479286_at 403 AA479286 ESTs 3.2 −3.54 J04111_at 624 J04111 v-jun avian sarcoma virus 17 oncogene homolog 3.2 −5.47 rc_AA465491_at 391 AA465491 Mad4 homolog 3.2 −2.75 W28548_at 997 W28548 ESTs 3.2 −3.59 AA308998_at 227 AA308998 endothelial differentiation-related factor 1 3.2 −2.89 rc_AA488432_at 412 AA488432 phosphoserine phosphatase 3.2 −3.48 rc_AA598991_at 430 AA598991 amyloid beta (A4) precursor protein-binding, 3.1 −4.51 family A, member 2 (X11-like) AA463311_at 384 AA463311 hypothetical protein similar to mouse Fbw5 3.1 −2.57 rc_AA147224_at 85 AA147224 ESTs 3.1 −4.41 rc_AA609504_at 444 AA609504 fibronectin leucine rich transmembrane protein 2 3.1 −3.81 U20734_s_at 952 U20734 jun B proto-oncogene 3.1 −3.37 U06863_at 941 U06863 follistatin-like 1 3.1 −2.48 W51743_at 1011 W51743 ESTs 3.1 −2.95 rc_AA465093_at 389 AA465093 TIA1 cytotoxic granule-associated RNA-binding 3.1 −5.34 protein rc_AA219100_at 132 AA219100 DKFZP586P2421 protein 3.1 −4.09 rc_R42424_at 832 R42424 ESTs 3.1 −3.82 rc_W73038_at 1026 W73038 ESTs 3.1 −2.23 AA091278_at 60 AA091278 hypothetical protein FLJ10793 3.1 −2.75 rc_AA620289_at 451 AA620289 PRO0518 protein 3.1 −2.55 rc_AA149579_at 87 AA149579 prostate cancer associated protein 1 3.1 −2.66 M21121_at 668 M21121 small inducible cytokine A5 (RANTES) 3.1 −4.97 rc_AA427890_at 312 AA427890 ESTs 3.1 −4.32 M34516_r_at 684 M34516 immunoglobulin lambda-like polypeptide 1 3.1 −3.47 rc_AA233347_at 140 AA233347 zinc finger protein 216 3.1 −2.43 rc_W74533_at 1029 W74533 latrophilin 3.1 −3.51 rc_AA029597_at 19 AA029597 bone morphogenetic protein 7 (osteogenic 3.1 −3.80 protein 1) rc_N91887_s_at 790 N91887 thymosin, beta, identified in neuroblastoma cells 3.1 −4.47 rc_AA205724_at 123 AA205724 ESTs 3.0 −6.70 U30521_at 960 U30521 P311 protein 3.0 −6.06 X07109_at 1052 X07109 protein kinase C, beta 1 3.0 −4.90 D82346_at 511 D82346 potassium voltage-gated channel, KQT-like 3.0 −3.49 subfamily, member 2 rc_AA478962_at 400 AA478962 ESTs 3.0 −3.35 rc_AA151428_s_at 90 AA151428 matrix metalloproteinase 23A, matrix 3.0 −2.78 metalloproteinase 23B rc_AA130349_at 73 AA130349 ESTs 3.0 −2.01 M18737_rna1_at 661 M18737 granzyme A (granzyme 1, cytotoxic T- 3.0 −5.90 lymphocyte-associated serine esterase 3) rc_N91461_at 789 N91461 ESTs 3.0 −3.43 rc_AA045481_at 30 AA045481 ESTs 3.0 −3.70 U91903_at 989 U91903 frizzled-related protein 3.0 −4.73 U19495_s_at 950 U19495 stromal cell-derived factor 1 3.0 −4.38 M33493_s_at 680 M33493 tryptase, alpha, tryptase, beta (tryptase II) 3.0 −3.12 Y12711_at 1103 Y12711 progesterone binding protein 3.0 −2.33 rc_N58172_at 757 N58172 ESTs 3.0 −2.53 M12529_at 655 M12529 apolipoprotein E 3.0 −1.92 rc_AA412505_at 288 AA412505 ESTs 3.0 −3.35 U45955_at 967 U45955 glycoprotein M6B 3.0 −4.09 rc_H56673_at 581 H56673 ESTs 3.0 −4.25 L33799_at 645 L33799 procollagen C-endopeptidase enhancer 3.0 −4.72 rc_Z40186_at 1114 Z40186 ESTs 3.0 −2.22 AA094800_at 64 AA094800 eukaryotic translation initiation factor 3, subunit 7 2.9 −2.56 (zeta, 66/67 kD) D21063_at 480 D21063 minichromosome maintenance deficient (S. 2.9 −5.27 cerevisiae) 2 (mitotin) rc_AA412049_at 284 AA412049 ESTs 2.9 −2.63 rc_AA599661_at 438 AA599661 ESTs 2.9 −8.62 L02870_s_at 633 L02870 collagen, type VII, alpha 1 (epidermolysis 2.9 −4.69 bullosa, dystrophic, dominant and recessive) rc_AA232266_s_at 138 AA232266 ESTs 2.9 −3.22 L02321_at 631 L02321 glutathione S-transferase M5 2.9 −3.33 rc_AA428325_at 315 AA428325 SEC14 (S. cerevisiae)-like 2 2.9 −3.52 D82534_at 512 D82534 f-box and leucine-rich repeat protein 5 2.9 −2.20 rc_T32113_at 889 T32113 KIAA0657 protein 2.9 −2.47 rc_R10896_at 808 R10896 cytochrome c oxidase subunit VIIa polypeptide 2 2.9 −1.99 like rc_AA019034_i_at 11 AA019034 ESTs 2.9 −4.40 D28423_at 485 D28423 ESTs 2.9 −2.31 rc_AA609943_at 449 AA609943 ESTs 2.9 −3.86 W69302_at 1023 W69302 ESTs 2.9 −2.68 rc_H01824_f_at 544 H01824 GATA-binding protein 2 2.9 −3.82 rc_T67105_s_at 910 T67105 ESTs 2.9 −5.49 rc_AA426372_s_at 307 AA426372 H1 histone family, member X 2.9 −2.53 rc_T98288_f_at 933 T98288 ESTs 2.9 −2.66 rc_N63047_at 762 N63047 ESTs 2.9 −5.25 U57316_at 974 U57316 GCN5 (general control of amino-acid synthesis, 2.9 −3.59 yeast, homolog)-like 2 rc_AA219304_s_at 133 AA219304 alpha-2-macroglobulin 2.9 −1.76

[0144] TABLE 4 Normal vs. BPH W/Symptoms Table (Down-regulated) SEQ ID Fold- Affymetrix element NO: GenBank ID GenBank Name change t rc_T40895_at 892 T40895 protein tyrosine phosphatase type IVA, member 16.5 5.19 1 rc_N80129_i_at 785 N80129 metallothionein 1L 12.6 3.54 rc_AA460914_at 380 AA460914 ESTs 7.4 4.58 rc_AA234996_s_at 147 AA234996 cytochrome C oxidase subunit VIa polypeptide 2 7.2 4.10 X66141_at 1078 X66141 myosin, light polypeptide 2, regulatory, cardiac, 6.6 3.80 slow AA234634_f_at 145 AA234634 CCAAT/enhancer binding protein (C/EBP), delta 6.2 4.35 rc_AA419011_at 296 AA419011 prostate androgen-regulated transcript 1 6.1 3.87 rc_N94303_at 797 N94303 ESTs 5.8 5.96 M20543_at 666 M20543 actin, alpha 1, skeletal muscle 5.5 3.20 rc_AA085943_s_at 58 AA085943 troponin T1, skeletal, slow 5.5 3.02 X06825_at 1050 X06825 tropomyosin 2 (beta) 5.2 3.35 AB000584_at 459 AB000584 prostate differentiation factor 5.1 3.80 M19309_s_at 665 M19309 troponin T1, skeletal, slow 5.0 3.41 rc_AA040433_at 24 AA040433 DKFZP586N2124 protein 5.0 2.62 rc_N32748_at 736 N32748 ESTs 5.0 3.36 rc_AA227926_at 135 AA227926 ESTs 4.8 5.39 rc_AA457566_at 375 AA457566 ESTs 4.7 4.22 rc_AA026641_s_at 16 AA026641 secretory leukocyte protease inhibitor 4.6 2.09 (antileukoproteinase) rc_AA053424_at 40 AA053424 serine/threonine protein kinase MASK 4.5 4.16 V00594_at 992 V00594 metallothionein 2A 4.5 3.71 rc_R16983_at 811 R16983 ESTs 4.5 3.23 U75272_s_at 984 U75272 progastricsin (pepsinogen C) 4.4 4.57 rc_T94447_s_at 928 T94447 cortic al thymocyte receptor (X. laevis CTX) like 4.4 3.50 U08021_at 942 U08021 nicotinamide N-methyltransferase 4.4 2.41 J03910_rna1_at 622 J03910 metallothionein 1G 4.3 2.79 rc_AA236545_at 156 AA236545 ESTs 4.2 2.41 rc_AA211443_at 127 AA211443 ESTs 4.2 4.49 rc_AA398908_at 251 AA398908 ESTs 4.2 2.64 X57129_at 1067 X57129 H1 histone family, member 2 4.2 3.88 M21665_s_at 670 M21665 myosin, heavy polypeptide 7, cardiac muscle, 4.1 3.61 beta X65614_at 1076 X65614 S100 calcium-binding protein P 4.1 4.03 rc_AA197112_r_at 119 AA197112 putative nuclear protein 4.1 3.07 M99487_at 716 M99487 folate hydrolase (prostate-specific membrane 4.0 2.65 antigen) 1 X04201_at 1045 X04201 neurotrophic tyrosine kinase, receptor, type 1 3.9 2.87 X05451_s_at 1046 X05451 ESTs 3.9 3.26 rc_AA435720_i_at 328 AA435720 tubulin, alpha 2 3.9 2.20 rc_N92502_s_at 794 N92502 ESTs 3.8 3.11 L77701_at 651 L77701 COX17 (yeast) homolog, cytochrome c oxidase 3.8 3.97 assembly protein HG2157-HT2227_at HG2157- ESTs 3.8 4.08 HT2227 X76717_at 1087 X76717 metallothionein 1L 3.8 5.82 HG1067-HT1067_r_at HG1067- ESTs 3.7 3.02 HT1067 rc_AA599331_at 433 AA599331 CGI-119 protein, uncharacterized bone marrow 3.6 4.90 protein BM039 M20642_s_at 667 M20642 ESTs 3.6 3.48 rc_AA055163_at 44 AA055163 calsequestrin 2, cardiac muscle 3.6 3.66 rc_AA127946_at 72 AA127946 DKFZP586B2022 protein 3.6 4.40 rc_AA022886_at 14 AA022886 retinal degeneration B beta 3.6 3.51 rc_AA342337_at 231 AA342337 ESTs 3.5 2.57 X02544_at 1042 X02544 orosomucoid 1 3.5 1.92 rc_T73433_s_at 912 T73433 angiotensinogen 3.5 3.10 M21494_at 669 M21494 creatine kinase, muscle 3.4 2.46 rc_AA488072_s_at 411 AA488072 cardiac ankyrin repeat protein 3.4 2.78 rc_AA293187_s_at 223 AA293187 B-cell CLL/lymphoma 3 3.4 1.62 rc_AA599522_r_at 437 AA599522 squamous cell carcinoma antigen recognised by 3.4 3.03 T cells rc_AA405488_at 268 AA405488 ESTs 3.4 2.57 rc_AA461453_at 382 AA461453 calcium binding protein Cab45 precursor, 3.4 3.10 rc_AA609006_at 440 AA609006 ESTs 3.4 2.30 rc_N24761_at 725 N24761 TU12B1-TY protein 3.4 3.89 rc_AA432162_at 324 AA432162 DKFZP586B2022 protein 3.4 2.78 X06256_at 1047 X06256 integrin, alpha 5 (fibronectin receptor, alpha 3.4 4.51 polypeptide) rc_AA045825_at 33 AA045825 ESTs 3.3 3.90 rc_AA478778_at 399 AA478778 ESTs 3.3 4.37 rc_N80129_f_at 785 N80129 metallothionein 1L 3.2 3.60 rc_AA182030_at 110 AA182030 pyruvate dehydrogenase kinase, isoenzyme 4 3.2 3.72 rc_AA102489_at 67 AA102489 hypothetical protein FLJ10337 3.2 2.20 rc_R46074_at 840 R46074 transforming, acidic coiled-coil containing protein 3.2 3.38 2 rc_AA599522_f_at 437 AA599522 squamous cell carcinoma antigen recognised by 3.2 2.36 T cells rc_AA165313_at 104 AA165313 ESTs 3.2 2.76 rc_AA429636_at 319 AA429636 hexokinase 2 3.2 3.12 rc_R71792_s_at 855 R71792 thrombospondin 1 3.1 2.31 U05861_at 940 U05861 aldo-keto reductase family 1, member C1 3.1 2.62 (dihydrodiol dehydrogenase 1; 20-alpha (3- alpha)-hydroxysteroid dehydrogenase), aldo-keto reductase family 1, member C2 (dihydrodiol dehydrogenase 2; bile acid binding protein; 3- alpha hydroxysteroid dehydrogenase, type III) rc_AA410311_at 275 AA410311 ESTs 3.1 3.52 rc_AA505136_at 426 AA505136 ESTs 3.1 3.00 rc_T68873_f_at 911 T68873 metallothionein 1L 3.0 3.18 X00371_ma1_at 1041 X00371 myoglobin 3.0 2.18 rc_AA099820_at 65 AA099820 ESTs 3.0 3.08 rc_T90190_s_at 925 T90190 H1 histone family, member 2 3.0 3.48 rc_AA227936_f_at 136 AA227936 parathymosin 3.0 1.76 X90568_at 1092 X90568 titin 3.0 2.83 rc_AA004699_at 1 AA004699 orphan G-protein coupled receptor 3.0 2.23 rc_F03969_at 528 F03969 ESTs 2.9 2.53 X93036_at 1093 X93036 FXYD domain-containing ion transport regulator 2.9 2.91 3 rc_R91484_at 863 R91484 ESTs 2.9 6.43 rc_AA025370_at 15 AA025370 K1AA0872 protein 2.9 2.87 X51441_s_at 1063 X51441 serum amyloid A1 2.9 1.78 X64177_f_at 1075 X64177 metallothionein 1H 2.9 3.36 rc_AA255480_at 173 AA255480 ECSIT 2.9 2.38 rc_AA476944_at 394 AA476944 ESTs 2.8 4.26 U78294_at 985 U78294 arachidonate 15-lipoxygenase, second type 2.8 1.82 rc_AA045487_at 31 AA045487 ESTs 2.8 2.75 rc_N74291_at 779 N74291 ESTs 2.8 1.88 rc_N91973_at 792 N91973 hypothetical protein,three prime repair 2.8 1.97 exonuclease 1 D81655_at 510 D81655 ESTs 2.8 1.89 U53225_at 971 U53225 sorting nexin 1 2.8 3.16 rc_H77597_f_at 594 H77597 metallothionein 1H 2.8 2.98 K02215_at 628 K02215 angiotensinogen 2.8 3.05 rc_AA464728_s_at 388 AA464728 ESTs 2.7 3.80 rc_W49708_at 1010 W49708 ESTs 2.7 3.52 rc_AA453435_at 364 AA453435 ESTs 2.7 4.78 rc_D11824_at 474 D11824 ESTs 2.7 3.70 rc_T56281_f_at 902 T56281 RNA helicase-related protein 2.7 2.62 rc_AA182882_at 111 AA182882 titin-cap (telethonin) 2.7 1.85 rc_AA447522_at 349 AA447522 ESTs 2.7 3.27 rc_N26904_at 731 N26904 FK506 binding protein precursor 2.7 3.21 rc_AA131919_at 75 AA131919 putative type II membrane protein 2.7 4.15 rc_R89840_at 862 R89840 ESTs 2.7 2.23 rc_W31470_at 998 W31470 thyroid hormone receptor-associated protein, 95- 2.7 2.85 kD subunit rc_W92207_at 1036 W92207 ESTs 2.7 4.07 U96094_at 990 U96094 sarcolipin 2.7 2.23 rc_W70131_at 1024 W70131 ESTs 2.7 3.64 rc_AA435720_f_at 328 AA435720 tubulin, alpha 2 2.7 1.98 rc_AA284879_at 212 AA284879 ESTs 2.7 1.74 rc_H22453_at 564 H22453 ESTs 2.7 4.20 D14826_s_at 478 D14826 cAMP responsive element modulator 2.6 4.13 rc_N93798_at 796 N93798 protein tyrosine phosphatase type IVA, member 2.6 3.12 3 U41804_at 965 U41804 putative T1/ST2 receptor binding protein 2.6 4.37 rc_W20486_f_at 995 W20486 chromosome 21 open reading frame 56 2.6 2.74 rc_AA055768_at 45 AA055768 CGI-119 protein 2.6 2.13 rc_AA447977_s_at 352 AA447977 ESTs 2.6 3.22 AA380393_at 243 AA380393 SEC7 homolog 2.6 2.29 rc_N29568_at 732 N29568 thyroid hormone receptor-associated protein, 2.6 2.46 150 kDa subunit rc_AA426374_f_at 308 AA426374 tubulin, alpha 2 2.6 3.20 rc_H94471_at 604 H94471 occludin 2.6 2.19 rc_AA252219_at 169 AA252219 ESTs 2.6 3.83 rc_AA402000_at 259 AA402000 ESTs 2.6 2.29 rc_Z38744_at 1108 Z38744 putative gene product 2.6 4.18 AA045870_at 34 AA045870 ESTs 2.6 2.26 rc_R38678_at 823 R38678 ESTs 2.6 4.16 R39467_f_at 826 R39467 NEU1 protein 2.6 2.79 AA455001_s_at 368 AA455001 CGI-43 protein 2.6 5.34 rc_AA292328_at 221 AA292328 activating transcription factor 5 2.6 2.88 X57348_s_at 1068 X57348 stratifin 2.6 2.48 rc_T95005_s_at 929 T95005 ESTs 2.5 3.30 AA410355_at 276 AA410355 ribosomal protein S6 kinase, 70 kD, polypeptide 2.5 2.31 AA036900_at 21 AA036900 ESTs 2.5 2.45 rc_F02204_at 521 F02204 BAI1-associated protein 2 2.5 2.26 U26173_s_at 958 U26173 nuclear factor, interleukin 3 regulated 2.5 3.91 rc_AA477767_at 396 AA477767 ESTs 2.5 3.17 rc_AA504805_s_at 424 AA504805 interferon stimulated gene (20 kD) 2.5 3.79 rc_R33627_i_at 818 R33627 ESTs 2.5 1.99 rc_T40995_f_at 893 T40995 alcohol dehydrogenase 3 (class I), gamma 2.5 2.15 polypeptide rc_R00144_at 801 R00144 ESTs 2.5 2.69 U02020_at 936 U02020 pre-B-cell colony-enhancing factor 2.5 4.20 rc_AA287832_at 217 AA287832 ESTs 2.5 3.80 AA429539_f_at 318 AA429539 hypothetical protein 2.5 2.35 rc_H05084_at 547 H05084 GDP-mannose pyrophosphorylase B 2.5 2.23 rc_AA405616_at 271 AA405616 ESTs 2.5 3.33 AA455381_at 370 AA455381 aldehyde dehydrogenase 5 family, member A1 2.4 2.60 (succinate-semialdehyde dehydrogenase) M13955_at 658 M13955 keratin 7 2.4 2.22 rc_AA180314_at 109 AA180314 ESTs 2.4 2.53 M37984_rna1_at 688 M37984 troponin C, slow 2.4 2.10 M61764_at 694 M61764 tubulin, gamma 1 2.4 3.48 rc_AA150920_at 88 AA150920 KIAA0539 gene product 2.4 4.11 X65965_s_at 1077 X65965 superoxide dismutase 2, mitochondrial 2.4 2.37 X93510_at 1094 X93510 LIM domain protein 2.4 2.39 rc_N48056_s_at 745 N48056 folate hydrolase (prostate-specific membrane 2.4 1.80 antigen) 1 rc_N26713_s_at 729 N26713 ESTs 2.4 3.87 rc_AA282247_at 204 AA282247 ESTs 2.4 3.17 rc_D80617_at 508 D80617 KIAA0596 protein 2.4 2.02 rc_F02245_at 522 F02245 monoamine oxidase A 2.4 2.79 rc_R58878_at 847 R58878 ESTs 2.4 2.80 rc_W45531_at 1007 W45531 ESTs 2.4 4.17 L25270_at 644 L25270 SMC (mouse) homolog, X chromosome 2.4 3.26 rc_W88568_at 1035 W88568 glycogenin 2 2.4 1.90 rc_AA070752_s_at 51 AA070752 insulin receptor substrate 1 2.4 2.87 U24169_at 956 U24169 JTV1 gene,hypothetical protein PRO0992 2.4 3.41 rc_T15423_s_at 878 T15423 2′,3′-cyclic nucleotide 3′ phosphodiesterase 2.4 1.71 X78706_at 1088 X78706 carnitine acetyltransferase 2.4 3.51 rc_T10695_i_at 876 T10695 enigma (LIM domain protein) 2.4 1.52 rc_AA430388_at 321 AA430388 HSPC160 protein 2.4 5.04 M68519_rna1_at 699 M68519 surfactant, pulmonary-associated protein A1 2.4 3.89 rc_AA421562_at 300 AA421562 anterior gradient 2 (Xenepus aevis) homolog 2.4 1.80 rc_T97243_at 931 T97243 prenyl protein protease RCE1 2.4 2.46 rc_T15409_f_at 877 T15409 ESTs 2.3 3.76 rc_T62918_at 905 T62918 ESTs 2.3 2.59 rc_R15108_at 810 R15108 ESTs 2.3 2.74 AA454908_s_at 366 AA454908 KIAA0144 gene product 2.3 2.77 rc_N64683_at 764 N64683 CGI-119 protein 2.3 2.27 rc_H99035_at 612 H99035 ESTs 2.3 4.34 Y08374_rna1_at 1100 Y08374 chitinase 3-like 1 (cartilage glycoprotein-39) 2.3 2.94 rc_AA236241_at 150 AA236241 ESTs 2.3 1.57 U52969_at 970 U52969 Purkinje cell protein 4 2.3 3.49 rc_R11526_f_at 809 R11526 parathymosin 2.3 1.71 rc_T15850_f_at 880 T15850 ESTs 2.3 2.42 HG2259-HT2348_s_at HG2259- tubulin, alpha 1 (testis specific), tubulin, alpha, 2.3 2.91 HT2348 ubiquitous rc_H15143_s_at 554 H15143 ortholog of rat pippin 2.3 1.45 rc_AA101767_at 66 AA101767 ESTs 2.3 3.52 rc_AA193197_at 116 AA193197 sarcomeric muscle protein 2.3 1.98 U03688_at 938 U03688 cytochrome P450, subfamily I (dioxin-inducible), 2.3 2.97 polypeptide 1 (glaucoma 3, primary infantile) rc_R37774_at 822 R37774 cytochrome P450 retinoid metabolizing protein 2.3 4.11 rc_H81413_f_at 597 H81413 high-mobility group (nonhistone chromosomal) 2.3 3.12 protein isoforms I and Y X16354_at 1060 X16354 carcinoembryonic antigen-related cell adhesion 2.3 2.54 molecule 1 (biliary glycoprotein) rc_AA457235_at 373 AA457235 ESTs 2.3 2.25 D13643_at 477 D13643 KIAA0018 gene product 2.3 1.78 rc_N30856_at 734 N30856 solute carrier family 19 (thiamine transporter), 2.3 3.45 member 2 M26311_s_at 673 M26311 S100 calcium-binding protein A9 (calgranulin B) 2.3 2.37 rc_Z40556_at 1116 Z40556 CGI-96 protein 2.3 2.39 rc_N79070_at 783 N79070 ESTs 2.3 1.43 Z69881_at 1122 Z69881 ATPase, Ca++ transporting, ubiquitous 2.3 3.87 rc_D60755_s_at 500 D60755 ESTs 2.3 2.30 rc_N94424_at 798 N94424 retinoic acid receptor responder (tazarotene 2.2 1.09 induced) 1

[0145] TABLE 5 Up-regulated genes Down-regulated genes Cluster Fragment Name Cluster Fragment Name 1 rc_AA256268_at 1 rc_AA227926_at 1 rc_AA188981_at 1 rc_AA398908_at 1 rc_AA173223_at 1 L77701_at 1 rc_AA216589_at 1 rc_AA599331_at 1 rc_AA234095_at 1 AA455001_s_at 1 rc_H17550_at 3 rc_AA022886_at 1 AA308998_at 3 rc_N24761_at 1 rc_AA488432_at 3 X06256_at 1 rc_AA427890_at 4 HG1067-HT1067_r_at 1 rc_N91887_s_at 4 rc_AA127946_at 1 rc_AA045481_at 4 rc_AA405488_at 3 rc_T23622_at 5 AA234634_f_at 3 rc_T23490_s_at 5 X65614_at 3 rc_AA620289_at 5 rc_T73433_s_at 4 rc_H05704_r_at 5 rc_R91484_at 4 rc_AA436616_at 5 rc_N93798_at 4 rc_AA456147_at 6 rc_N94303_at 4 rc_f09748_s_at, AA495865_at 6 AB000584_at 4 rc_AA598982_s_at 6 rc_AA410311_at 4 HG3543-HT3739 at 6 rc_F02245_at 4 rc_AA609504_at 7 rc_T40895_at 5 rc_AA028092_s_at 7 rc_N80129_i_at, X76717_at rc_N80129_f_at, rc_T68873_f_at 5 U62015_at 7 rc_N32748_at 5 rc_F13763_at 7 V00594_at 5 rc_AA205724_at 7 J03910_rnal_at 5 U30521_at 7 X57129_at, rc_T90190_s_at 6 X52541_at 7 rc_AA182030_at 6 rc_AA281345_f_at, M62831_at 7 rc_AA505136_at 7 rc_n22006_s_at 7 X64177_f_at, rc_H77597_f_at 7 rc_R42424_at 7 rc_AA101767_at

[0146] TABLE 6 BPH vs. Normal and Cancer P-Values Normal Normal Normal BPHWS BPHWS BPHNoS Affymetrix SEQ ID vs. vs. vs. vs. vs. vs. Fragment Name NO: GenBank ID GenBank Name BPHWS BPHNoS Cancer BPHNoS Cancer Cancer AA092215_at 61 AA092215 potassium channel 0.1086431 0.887604969 0.000105867 0.141381127 0.031099165 0.000775399 modulatory factor AA122242_at 70 AA122242 mannose-6-phosphate 7.49E-05 0.560180168 0.87992066 0.006231736 0.000301953 0.664273011 receptor (cation dependant) AA122302_at 71 AA122302 0.430127474 0.003373118 0.068806262 0.000514723 0.328161735 1.48715E-05 AA155958_at 94 AA155958 S164 protein 0.096247016 0.007959573 0.170003368 8.36688E-05 0.782399153 0.000223021 AA236286_at 151 AA236286 fetal Alzheimer antigen 0.052450894 0.034104742 0.076032207 0.000262856 0.875443134 0.000444882 AA248802_at 165 AA248802 DKFZP564A122 protein 0.000230259 0.38257085 0.842458286 0.026030678 0.000947368 0.500601376 AA293544_at 225 AA293544 D component of 7.02821E-05 0.203858328 0.178154822 5.9415E-06 0.012632481 0.019226603 complement (adipsin) AA376488_at 242 AA376468 0.405364589 0.000353844 0.537460601 0.006147013 0.169320077 7.97148E-05 AA410925_at 278 AA410925 transducin-like enhancer 0.870505598 1.09859E-05 0.106359333 4.33855E-05 0.168431987 0.003967521 of split 1, homolog of Drosophila E(sp1) AA461618_s_at 383 AA461618 0.001614433 0.497688178 0.000768417 0.001055794 6.29856E-10 0.031759146 C15965_at 468 C15965 0.000459149 0.350724893 0.919693498 0.000138025 0.000627643 0.416397432 D10537_s_at 472 D10537 myelin protein zero 4.11477E-05 0.923679005 4.72641E-05 0.000899706 0.975645863 0.00098994 (Charcot-Marie-Tooth neuropathy 1B) D25303_at 482 D25303 integrin, alpha 9 0.00061935 0.196221991 0.000846365 0.108182462 0.935105808 0.124782864 D26598_at 483 D26598 proteasome (prosome, 0.000121781 0.02105211 8.45942E-05 0.326778603 0.933101073 0.291769938 macropain) subunit, beta type, 3 D31887_at 489 D31887 K1AA0062 protein 0.000123265 0.125782983 0.000676946 0.084742928 0.675822922 0.174766454 D50532_at 492 D50532 macrophage lectin 2 0.013806312 0.034992941 0.07897755 0.981647465 6.26998E-05 0.000487842 (calcium dependent) D50550_at 493 D50550 lethal giant larvae 3.10455E-05 0.029363545 4.06139E-05 0.169772872 0.953324091 0.186302331 (Drosophila) homolog 1 D64154_at 503 D64154 cell membrane 1.68633E-05 0.000696104 5.008732-05 0.747380424 0.814285971 0.90759386 glycoprotein, 110000M(r) (surface antigen) D84294_at 514 D84294 tetratricopeptide repeat 8.04076E-06 0.163620727 0.000752223 0.017501269 0.299205599 0.142785528 domain 3 D86976_at 515 D86976 minor histocompatibility 3.35538E-06 0.219311742 4.36833E-07 0.007209475 0.701246025 0.002498824 antigen HA-1 D87258_at 516 D87258 protease, serine, 11 (IGF 9.00737E-05 0.762310231 0.004565624 0.000386998 0.305696637 0.008038934 binding) D87292_at 517 D87292 thiosulfate 0.004418719 0.000188241 0.000878154 0.222741306 0.648642702 0.412420863 sulfurtransferase (rhodanese) D87465_at 518 D87465 KIAA0275 gene product 7.37644E-05 0.826724125 0.000140053 0.000450807 0.882546967 0.000727958 H19969_at 562 H19969 0.005160656 7.47697E-07 6.71287E-07 0.01521142 0.039287107 0.535558762 H61361_s_at 587 H61361 immunoglobulin 4.92249E-05 0.834280925 5.95931E-05 0.001490555 0.966053313 0.001694157 superfamily containing leucine-rich repeat J00277_at 618 J00277 v-Ha-ras Harvey rat 0.035655118 0.055426457 0.009927846 0.000332747 0.650555821 6.72893E-05 sarcoma viral oncogene homolog J04076_at 623 J04076 early growth response 2 0.034912914 0.473833846 2.46869E-11 0.285997211 1.48067E-05 1.13903E-06 (Krox-20 (Drosophila) homolog) J04605_at 627 J04605 peptidase D 0.000200727 0.006030981 0.000362209 0.648903631 0.885410388 0.742239283 K03204_f_at 630 K03204 proline-rich protein BstNI 0.283795673 0.000798814 0.913648897 0.019814734 0.26284107 0.000926711 subfamily 1 L02326_f_at 632 L02326 0.105345943 0.659037818 6.62426E-05 0.076492051 0.02455672 0.000181614 L05500_at 635 L05500 adenylate cyclase 1 0.016699778 0.257619651 3.79921E-05 0.002077455 0.101519111 6.32745E-06 (brain) L06797_s_at 636 L06797 chemokine (C-X-C 0.443118956 0.447152817 1.30523E-06 0.926525008 0.000111977 0.000981046 motif), receptor 4 (fusin) L08246_at 637 L08246 myeloid cell leukemia 0.043208838 0.230033308 4.68128E-10 0.596833839 6.55684E-05 5.57731E-05 sequence 1 (BCL2- related) L13740_at 639 L13740 nuclear receptor 0.791312753 0.872331125 8.60985E-05 0.70798804 7.00025E-05 0.001852799 subfamily 4, group A, member 1 L13852_at 640 L13852 ubiquitin-activating 0.000578096 0.646204921 0.003882395 0.000950816 0.599103668 0.004460291 enzyme E1-like L19437_at 641 L19437 transaldolase 1 0.008021968 0.22883538 0.001388037 0.000773689 0.604482478 0.000135454 L34587_at 646 L34587 transcription elongation 0.000178315 0.105125832 7.09176E-05 0.11839964 0.830767426 0.080296411 factor B (SIII), polypeptide 1 (15 kD, elongin C) L44497_at 648 L44497 cyclic AMP 0.000816364 0.012044336 0.000161685 0.709380948 0.686659704 0.467540879 phosphoprotein, 19 kD L76200_at 650 L76200 guanylate kinase 1 0.000841699 0.002396122 0.000888336 0.889388751 0.988638065 0.879528075 M12959_s_at 656 M12959 T cell receptor alpha 3.02601E-08 0.817611534 3.24058E-08 1.14437E-05 0.990909384 1.1981E-05 locus M13560_s_at 657 M13560 CD74 antigen (invariant 0.01541788 0.255419127 4.82527E-06 0.001882075 0.041399052 9.73079E-07 polypeptide of major histocompatibility complex, class II antigen- associated) M14660_at 659 M14660 1.95092E-06 0.823404837 0.009910008 0.000180501 0.038673415 0.053432817 M16336_s_at 660 M16336 CD2 antigen (p50), 0.000908965 0.444045616 0.000106508 0.042888317 0.596564762 0.01280799 sheep red blood cell receptor M19154_at 663 M19154 transforming growth 0.021033675 0.886661499 5.38416E-05 0.039706043 0.100571645 0.00047052 factor, beta 2 M19283_at 664 M19283 actin, gamma 1 0.009680549 0.975542421 1.35524E-05 0.029109597 0.094241798 0.000262549 M21121_s_at 668 M21121 small inducible cytokine 0.00011935 0.82444906 0.028900951 0.000639223 0.114726075 0.042253328 A5 (RANTES) M31776_s_at 677 M31776 natriuretic peptide 9.53305E-05 0.786764461 0.00132485 0.000453681 0.511730949 0.003376181 precursor B M33552_at 681 M33552 lymphocyte-specific 0.098325681 0.187562681 0.000373789 0.008253387 0.070738695 2.37353E-05 protein 1 M37766_at 687 M37766 CD48 antigen (B-cell 0.006750544 0.671986725 0.000173892 0.007796504 0.321364096 0.000414775 membrane protein) M54927_at 689 M54927 proteolipid protein 0.0008203 0.071504547 0.000610665 0.292633338 0.938762949 0.26282367 (Pelizaeus-Merzbacher disease, spastic paraplegia 2, uncomplicated) M59465_at 691 M59465 tumor necrosis factor, 0.905275899 0.300604716 2.40334E-05 0.370512119 3.79139E-05 6.51796E-06 alpha-induced protein 3 M60459_at 693 M60459 erythropoietin receptor 5.33228E-07 0.001997812 2.00307E-06 0.229150396 0.804556624 0.324369463 M73077_at 701 M73077 glucocorticoid receptor 4.33165E-05 0.026210722 7.3229E-05 0.205361352 0.906734945 0.244557908 DNA binding factor 1 M89796_rna1_at 705 M89796 membrane-spanning 4- 3.38097E-07 0.68414038 0.000659504 0.000116527 0.107834095 0.014565483 domains, subfamily A, member 1 M94077_at 709 M94077 loricrin 7.86788E-05 0.167396165 8.55841E-06 0.050135902 0.633682729 0.017465235 M94547_at 710 M94547 myosin light chain 2a 0.000922884 0.001567598 0.000142192 0.778547965 0.641162082 0.898495047 M95678_at 712 M95678 phospholipase C, beta 2 2.65752E-06 0.741444839 0.00021566 0.000330645 0.344847831 0.005753116 M96995_5_at 713 M96995 growth factor receptor- 0.000451432 0.370687613 0.000417356 0.039514013 0.984237779 0.037882757 bound protein 2 M98447_rna1_at 714 M98447 transglutaminase 1 (K 0.101078475 0.000501168 0.49866517 0.047778543 0.027993512 9.36193E-05 polypeptide epidermal type I, protein-glutamine- gamma- glutamyltransferase) N24990_a_at 728 N24990 0.000594989 0.692375474 0.833157714 0.001206749 0.00054518 0.837698657 R08720_at 805 R08720 hypothetical protein 0.384088189 0.004709624 0.405658837 0.000582614 0.970613897 0.000656156 FLJ22609 R33301_at 817 R33301 0.263328276 0.008898636 0.324726425 0.000573184 0.899017203 0.000860093 R39394_at 825 R39394 E1B-55kDa-associated 0.000120098 0.168965093 0.159597216 5.8721E-06 0.020650662 0.012378795 protein 5 rc_AA004901_at 2 AA004901 0.00013 0.114226367 0.898931127 2.58485E-06 0.000448774 0.104547963 rc_AA005382_s_at 3 AA005382 granzyme K (serine 4.06793E-05 0.956799991 0.000100487 0.000772831 0.838991074 0.001451838 protease, granzyme 3; tryptase II) rc_AA009615_at 5 AA009615 7.69548E-05 0.013016412 0.000583037 0.366115762 0.625611179 0.634185041 rc_AA010358_at 7 AA010358 1.36211E-06 0.550401822 0.139035486 0.000570081 0.001477269 0.511053692 rc_AA017547_r_at 9 AA017547 hypothetical protein 0.989540408 0.214430361 0.000274727 0.228713943 0.000584071 2.44522E-05 FLJ12387 similar to kinesin light chain rc_AA018414_at 10 AA018414 0.556560157 0.000998026 0.519992597 0.000261037 0.958086097 0.000217926 rc_AA022615_at 13 AA022615 RNA binding motif 0.000158793 0.509341291 0.263342589 0.000159018 0.011670476 0.117665916 protein 9 rc_AA037828_at 22 AA037828 0.000583981 0.645542969 0.84290982 0.000955558 0.002108779 0.543978545 rc_AA043196_at 26 AA043196 SMC (mouse) homolog, 0.008527895 0.000983583 0.000257323 0.328438436 0.331116816 0.90061816 X chromosome rc_AA053267_at 39 AA053267 K1AA1023 protein 0.000119181 0.288536772 0.388296579 2.42934E-05 0.004627114 0.082295734 rc_AA053883_at 41 AA053883 4.95718E-05 0.962839667 0.16054889 0.000624096 0.01179586 0.225390364 rc_AA054222_at 42 AA054222 0.39176403 0.002571399 0.102566251 0.000307234 0.461555799 2.09152E-05 rc_AA055081_at 43 AA055081 6.36828E-05 0.206434411 0.797911434 5.59851E-06 5.42681E-05 0.316914958 rc_AA065173_at 49 AA065173 chromosome 5 open 2.526782-07 0.570857861 0.058275966 0.000180212 0.001970189 0.302526217 reading frame 4 rc_AA069913_at 50 AA069913 0.653765843 0.52776555 5.65709E-06 0.815416554 0.000104293 0.00152505 rc_AA071558_at 52 AA071558 0.168309619 0.418677904 0.000189452 0.054446269 0.025471654 0.000103274 rc_AA082041_at 53 AA082041 likely homolog of rat 0.000143369 0.247732655 0.871515758 0.040056839 0.000552895 0.3290855 kinase 0-interacting substance of 220 kDa; KIAA1250 protein rc_AA084324_at 56 AA084324 0.000226203 0.056433291 0.000687497 0.216607531 0.780835192 0.321404997 rc_AA085608_at 57 AA085608 KIAA1041 protein 0.029391584 0.03435634 0.041546789 0.000120442 0.894217078 0.000192545 rc_AA114858_at 68 AA114858 tyrosine 3- 0.000210292 0.155417252 0.994165585 8.636522-06 0.000449478 0.170373425 monooxygenase/tryptoph an 5-monooxygenase activation protein, eta polypeptide rc_AA132239_at 76 AA132239 0.012168107 5.56988E-05 4.55236E-05 0.074087524 0.136307788 0.631558319 rc_AA132453_at 77 AA132453 0.000489304 0.141814616 8.74406E-05 0.136343527 0.678807616 0.063921338 rc_AA138864_at 81 AA136864 zinc finger protein 0.000224205 0.630168118 4.90412-05 0.009114985 0.72551107 0.003549498 homologous to Zfp-36 in mouse rc_AA143190_s_at 83 AA143190 CGI-147 protein 5.316942-05 0.028242427 0.000127165 0.209594394 0.842566905 0.279924929 rc_AA143467_at 84 AA143467 hypothetical protein 1.62361E-06 0.259338862 1.37865E-06 0.003657312 0.975267724 0.003351742 FLJ20343 rc_AA149051_at 86 AA149051 4.08493E-05 0.490333235 0.026825837 4.57567E-05 0.07318676 0.012248149 rc_AA152408_at 93 AA152408 K1AA0433 protein 2.97974E-05 0.362537361 0.455914763 1.36986E-05 0.001140199 0.13486533 rc_AA156064_at 95 AA156064 0.275270351 0.000333624 0.875633108 0.011111677 0.23661308 0.000347347 rc_AA158132_at 98 AA158132 nudix (nucleoside 0.004899515 0.643469716 4.65182E-07 0.057915819 0.034659352 0.000177571 diphosphate linked moiety X)-type motifs rc_AA165116_at 101 AA165116 0.000334885 0.681603266 0.211571862 0.000813512 0.029042963 0.151679697 rc_AA165231_at 102 AA165231 0.002549485 0.173959444 0.254670513 0.000135147 8.0406E-05 0.719982481 rc_AA169837_at 105 AA169837 NADH dehydrogenase 0.08971279 0.008766485 0.091371238 8.4903E-05 0.993409911 8.74977E-05 (ubiquinone) Fe-S protein 6 (13 kD) (NADH- coenzyme Q reductase) rc_AA172188_at 107 AA172188 protocadherin alpha 5 0.000667976 0.267150381 4.96881E-06 0.077589163 0.269599078 0.006273958 rc_AA189015_at 113 AA189015 aminolevulinate, delta-, 0.083660421 0.006384313 1.64695E-08 0.237580015 0.000203416 0.037803249 synthase 2 (sideroblastic/hypochromic anemia) rc_AA192553_at 115 AA192553 uncoupling protein 3 0.10098208 0.00017981 0.933630822 0.02546947 0.102059527 0.000244309 (mitochondrial, proton carrier) rc_AA196549_at 118 AA196549 0.001049824 0.569766558 0.000482225 0.001065463 0.839463674 0.000559925 rc_AA205072_at 120 AA205072 KIAA0980 protein 0.000335755 0.586934845 0.684865398 0.000455367 0.002552925 0.389985886 rc_AA205460_at 122 AA205460 0.000108573 0.165439416 0.84259483 5.28568E-06 0.000494762 0.134180366 rc_AA205947_at 124 AA205947 HHGP protein 0.000271962 0.552878143 0.70583219 0.000318994 0.001963327 0.376568675 rc_AA207103_at 125 AA207103 amiloride-sensitive cation 2.053312-05 0.045239142 0.642629872 0.10526525 0.000317921 0.124103707 channel 2, neuronal rc_AA211300_at 126 AA211300 KIAA0627 protein; 0.004445798 0.287777463 0.006200387 0.000703498 0.918638362 0.000971608 Drosophila “multiple asters”(Mast)-like homolog 2 rc_AA211835_s_at 128 AA211835 MHC class II 0.001672055 0.122505424 0.000371358 4.15083E-05 0.692673582 8.76636E-06 transactivator rc_AA215379_at 130 AA215379 7.98828E-05 0.366787682 0.194666913 3.33447E-05 0.012005727 0.051632715 rc_AA228020_at 137 AA228020 splicing factor (CC1.3) 0.00047128 0.328754864 0.940819016 0.000119264 0.001167483 0.317270472 rc_AA233545_at 141 AA233545 AD-003 protein 0.004492717 0.655215048 2.53288E-07 0.052976799 0.028149978 0.000113193 rc_AA233854_at 142 AA233854 S-phase kinase- 3.799S4E-05 0.744241299 0.538817385 0.001845337 0.000884538 0.84309443 associated protein 2 (p45) rc_AA233935_at 143 AA233935 0.000608235 0.578078963 0.30216801 0.00070772 0.023016587 0.163656536 rc_AA234631_at 146 AA234631 KIAA0788 protein 0.000575081 0.410892837 0.954178902 0.000257285 0.000897188 0.457935122 rc_AA236453_at 152 AA236453 0.036687413 0.061484767 0.023140149 0.000407818 0.863002571 0.000227528 rc_AA236477_at 155 AA236477 KIAA1559 protein 0.000207423 0.453577644 0.288868663 0.000140775 0.011962605 0.1090363 rc_AA236822_at 157 AA236822 KIAA1097 protein 0.008052957 0.439727961 0.000891185 0.003207259 0.52319673 0.000453056 rc_AA237011_at 158 AA237011 ATP-binding cassette, 0.000202964 0.000263744 1.87304E-06 0.678815593 0.318565402 0.645008985 sub-family F (GCN20), member 1 rc_AA237034_at 159 AA237034 golgi SNAP receptor 2.31824E-05 0.319635059 3.30639E-08 0.010320292 0.220104139 0.000272212 complex member 2 rc_AA243416_s_at 180 AA243416 hypothetical protein, 0.033376619 4.72108E-05 0.469143753 0.032420785 0.182985166 0.000942701 expressed in osteoblast rc_AA243698_at 161 AA243698 potassium channel 0.06151528 0.302492952 0.000486853 0.010884151 0.124764794 9.91149E-05 modulatory factor rc_AA243763_at 162 AA243763 0.050706904 0.01206437 0.11555761 5.40095E-05 0.71829242 0.000198301 rc_AA253361_at 172 AA253361 0.000564229 0.000110501 0.010769519 0.397832434 0.394174789 0.11120186 rc_AA255966_at 174 AA255966 0.000512371 0.381782918 0.000368364 0.040324542 0.933794518 0.03373143 rc_AA256486_at 177 AA256486 CGI-141 protein 0.053041853 0.519681482 0.000805238 0.025864118 0.179038095 0.000657368 rc_AA258585_at 180 AA258585 cadherin 19, type 2 8.77783E-08 0.008879695 3.84529E-06 0.0526509 0.488129443 0.183610463 rc_AA258595_f_at 181 AA258595 major histocompatibility 0.056902737 0.411462581 1.12504E-05 0.017626477 0.018278908 8.86477E-06 complex, class II, DQ beta 1 rc_AA262107_at 183 AA262107 0.051109951 0.028221779 0.046925687 0.000190669 0.972441626 0.000168986 rc_AA262349_at 184 AA262349 hypothetical protein 0.023368538 0.075191389 0.000520191 0.000323092 0.25384504 4.28987E-06 FLJ10628 rc_AA262477_at 185 AA262477 ribonuclease HI, large 0.843423091 0.000293418 0.145801246 0.000917609 0.233064808 0.023283635 subunit rc_AA262969_f_at 186 AA262969 px19-like protein 0.000697965 0.002321008 4.86461E-08 0.916139727 0.050019001 0.106622452 rc_AA278757_at 187 AA278757 KIAA1205 protein 0.000807747 0.701913497 0.00019298 0.001603897 0.719959281 0.000521168 rc_AA278887_at 189 AA278887 4.77289E-05 0.000505266 0.002921534 0.966491221 0.300838621 0.386804461 rc_AA279028_at 190 AA279028 0.269683575 0.000110029 0.896242284 0.00515459 0.355782598 0.000309622 rc_AA279774_at 194 AA279774 0.028330552 0.004250917 0.09766388 4.84994E-06 0.610845854 3.70943E-05 rc_AA279821_s_at 195 AA279821 0.01541818 0.057056528 0.036000999 0.00012115 0.75748484 0.000352962 rc_AA280297_at 196 AA280297 0.004904401 0.069649547 0.030554618 4.43102E-05 0.537205763 0.000396218 rc_AA280309_at 197 AA280309 0.027919295 0.048777883 0.042451847 0.000197325 0.872357649 0.000341621 rc_AA280617_at 198 AA280617 0.020747951 0.100016813 0.006218315 0.000457645 0.687853962 0.000114895 rc_AA282739_at 205 AA282739 Ser/Arg-related nuclear 0.006885251 0.224885918 0.001928329 0.000638964 0.705244944 0.000179491 matrix protein (plenty of prolines 101-like) rc_AA283091_at 206 AA283091 KIAA1219 protein 0.000391955 0.950383286 0.000147487 0.003849943 0.812656175 0.001947884 rc_AA283772_at 207 AA283772 replication factor C 0.472125644 0.004274231 0.126899001 0.00082772 0.443684418 5.94032E-05 (activator 1) 5 (36.5kD) rc_AA283774_at 208 AA283774 0.634799287 0.001085136 0.774459677 0.000408559 0.858121118 0.000730937 rc_AA283907_at 209 AA283907 DC12 protein 0.702306606 0.426110345 0.000364953 0.278959611 0.000181185 0.027738884 rc_AA284777_at 211 AA284777 0.00028958 0.613024306 0.843581256 0.0004624 0.001148934 0.515630593 rc_AA286862_at 214 AA286862 WD repeat domain 6 0.006465478 0.770956466 3.90332E-06 0.047019059 0.072475744 0.000368843 rc_AA287107_s_at 215 AA287107 zinc finger protein 0.000557513 0.647966939 0.168481176 0.000931348 0.049075778 0.113081619 ZNF140-like protein rc_AA287870_s_at 218 AA287870 lymphotoxin beta (TNF 0.042868875 0.904123896 4.72641E-06 0.071763173 0.015492602 8.72095E-05 superfamily, member 3) rc_AA291970_at 220 AA291970 lectomedin-2 0.133517759 0.00116479 0.062658963 1.25187E-05 0.731829127 3.02794E-06 rc_AA292533_at 222 AA292533 putative Rab5-interacting 8.63268E-05 0.143959708 1.94797E-06 0.062483153 0.429586131 0.010599279 protein rc_AA342918_at 232 AA342918 hypothetical protein 0.000298568 0.534260232 0.802167146 0.015864864 0.000243847 0.42047475 FLJ22313 rc_AA347578_at 234 AA347578 tubulin, beta polypeptide 0.056066605 0.067322154 0.053415125 0.000815763 0.984081099 0.000765743 rc_AA348446_at 235 AA348446 0.00081514 0.498461887 0.002492252 0.000590962 0.75904915 0.001541743 rc_AA349417_at 236 AA349417 0.333508877 4.09468E-05 0.860387174 0.001709823 0.452900772 0.000147762 rc_AA370867_at 239 AA370867 0.000438073 0.000509149 0.076534621 0.678852203 0.097859647 0.062063558 rc_AA371520_at 240 AA371520 0.000956188 0.182406672 0.0004497 0.142299266 0.84509761 0.101288353 rc_AA398719_at 249 AA398719 homolog of rat nadrin 0.005171893 0.312848506 0.003453438 0.000980065 0.903295813 0.000667115 rc_AA399101_at 252 AA399101 0.020406213 0.066006562 0.014033951 0.000219359 0.896140692 0.00013891 rc_AA399542_f_at 254 AA399542 0.225479535 0.502403493 5.62157E-05 0.098347881 0.007549959 6.44137E-05 rc_AA400034_at 255 AA400034 0.250995551 0.01453561 0.033099094 0.00095651 0.35107658 3.77436E-05 rc_AA401297_s_at 256 AA401297 symplekin; Huntingtin 0.012585329 0.166831042 0.004370096 0.000663018 0.73639502 0.000215874 interacting protein I rc_AA402468_at 261 AA402468 0.099732216 9.36987E-05 0.673315411 0.017152495 0.245352826 0.000668187 rc_AA402473_at 262 AA402473 0.457960224 0.000426525 0.079152517 6.26915E-05 0.336346183 1.26194E-06 rc_AA405331_at 267 AA405331 golgi autoantigen, golgin 0.586184325 0.001885183 0.429082537 0.000584353 0.815182938 0.00026866 subfamily a, 5 rc_AA405533_at 269 AA405533 integral membrane 0.000172614 0.497994468 0.082141472 0.000159183 0.055604922 0.0359498 protein 2B rc_AA405902_at 272 AA405902 0.086820061 0.039035914 0.014052865 0.000655228 0.480598833 5.66656E-05 rc_AA410954_at 279 AA410954 1.16178E-05 1.50623E-06 1.03048E-05 0.330330235 0.980294091 0.341205824 rc_AA411897_at 281 AA411897 0.508186682 0.001994491 0.445499823 0.00043102 0.923458644 0.000312647 rc_AA412267_at 286 AA412267 0.164103629 3.89169E-07 0.756068057 1.61111E-09 0.10637429 3.90003E-06 rc_AA412443_at 287 AA412443 0.364026646 0.005904843 0.355261504 0.000673161 0.987349969 0.000639721 rc_AA417011_at 292 AA417011 0.97881335 0.000103601 0.347607058 0.000209225 0.359543109 6.44615E-06 rc_AA417348_at 293 AA417348 0.011726682 0.000513628 0.000733098 0.214868351 0.416407972 0.597824364 rc_AA417915_at 294 AA417915 0.00031475 0.724609869 0.33434685 0.000849216 0.012345648 0.253561808 rc_AA418557_at 295 AA418557 0.228039568 0.580130356 0.000535144 0.124915173 0.032252409 0.000643742 rc_AA421131_at 298 AA421131 0.000944552 0.385647564 0.015545606 0.00033745 0.400009139 0.00441922 rc_AA421133_at 299 AA421133 erythrocyte 0.048370115 0.776945443 3.5594E-06 0.170573072 0.011573179 0.000337276 transmembrane protein rc_AA424037_s_at 301 AA424037 0.004243716 0.739593135 2.30322E-05 0.006963992 0.192467998 0.000122214 rc_AA424245_at 302 AA424245 0.000912849 0.241386195 0.000608875 0.10233451 0.915105608 0.08414343 rc_AA424515_at 303 AA424515 0.001461647 0.327161944 0.557700471 0.000331758 0.000350136 0.650111174 rc_AA425325_at 305 AA425325 0.000137613 0.761000474 0.006888125 0.000531496 0.292230161 0.011066086 rc_AA425354_at 306 AA425354 1.135E-05 0.848812392 4.31696E-05 0.000125249 0.776028887 0.000335665 rc_AA426438_at 309 AA426438 tissue factor pathway 0.086215951 0.051460629 0.077775438 0.000971113 0.963651921 0.000841613 inhibitor (lipopretein- associated coagulation inhibitor) rc_AA426454_s_at 310 AA426454 imidazoline receptor 4.93792E-06 0.168883843 0.000430545 0.013194044 0.320673843 0.1079437 candidate rc_AA427944_at 313 AA427944 0.016580683 2.63482E-05 0.961128446 0.040898728 0.020386125 4.53083E-05 rc_AA428243_at 314 AA428243 integrin beta 4 binding 0.000258966 0.030169371 0.000115376 0.338639919 0.847641147 0.260434676 protein rc_AA428460_at 316 AA428460 0.369406205 2.86818E-05 0.170103625 1.87552E-06 0.031318989 0.00400089 rc_AA429398_s_at 317 AA429398 0.042509423 0.318204908 0.000808205 0.00812556 0.209966492 0.000179435 rc_AA430738_at 322 AA430738 hypothetical protein 2.4223E-05 0.512347676 0.057495876 3.43792E-05 0.027579258 0.027106503 FLJ22693 rc_AA433922_at 326 AA433922 NRAS-related gene 0.000129534 0.750927276 0.024589837 0.000483913 0.13400345 0.02912486 rc_AA435753_at 329 AA435753 0.167368191 0.01678153 0.00563702 0.000567982 0.188083313 4.20658E-06 rc_AA435852_at 331 AA435852 hypothetical protein 0.000178813 0.813799408 0.130706548 0.000825341 0.033909282 0.137866512 rc_AA436244_at 332 AA436244 0.000347902 0.773066458 0.838936155 0.006955308 0.000335763 0.655473596 rc_AA436489_at 333 AA436489 dual specificity 0.089585972 0.000336423 0.53802583 0.042116461 0.028187175 7.58265E-05 phosphatase 10 rc_AA436548_at 334 AA436548 4.79946E-05 0.79712195 0.073989554 0.000284052 0.03065051 0.082990101 rc_AA436823_at 338 AA436823 3.43729E-06 0.007238466 0.000134014 0.199586541 0.434475995 0.550333062 rc_AA436841_at 339 AA436841 nuclear factor of kappa 0.000757034 0.109130693 3.14861E-05 0.206545207 0.451070087 0.054341855 light polypeptide gene enhancer in B-cells inhibitor, beta rc_AA437226_s_at 341 AA437226 interleukin 10 receptor, 0.030634205 0.394007384 3.12463E-06 0.008853685 0.017676075 2.623E-06 alpha rc_AA442830_at 342 AA442830 0.277387057 0.000957882 0.739163222 4.56542E-05 0.474861158 0.000560401 rc_AA446899_at 348 AA446899 mannosidase, alpha, 4.08376E-08 0.474845978 8.66417E-09 0.000104871 0.799444331 4.09828E-05 class 1B, member 1 rc_AA448228_at 353 AA448228 HSPC142 protein 0.489815716 0.427628808 0.00011718 0.181303904 1.63664E-05 0.014570459 rc_AA450073_s_at 357 AA450073 paired mesoderm homeo 0.070060208 0.424331633 0.00057893 0.02291416 0.12207024 0.000282414 box 1 rc_AA450373_at 361 AA450373 0.19184076 0.000421707 3.75092E-05 0.021344923 0.007526828 0.966348045 rc_AA454016_at 365 AA454016 0.74223808 0.000765848 0.794392558 0.003084476 0.575990681 0.000561238 rc_AA454928_at 367 AA454928 phosphorylase kinase, 0.042150436 0.023733581 0.157838834 0.000111797 0.556629171 0.000814363 beta rc_AA457148_at 372 AA457148 0.770822781 0.643699605 7.37551E-05 0.492232725 0.000493842 0.00082201 rc_AA457407_at 374 AA457407 transmembrane 0.322389783 0.009487182 0.088848624 0.000914536 0.499415786 9.30818E-05 protease, serine 2 rc_AA457675_at 376 AA457675 0.000470812 0.007879992 0.000974653 0.721378015 0.850190113 0.848554875 rc_AA459272_at 377 AA459272 8.59013E-05 0.738589634 0.711426345 0.003207799 0.00073865 0.989771621 rc_AA460377_at 378 AA460377 beta-catenin-interacting 0.015059101 0.036482503 0.009644184 5.52729E-05 0.881315511 3.13984E-05 protein ICAT rc_AA464598_at 387 AA464598 KIAA1389 protein 0.000373603 0.650628457 0.000200085 0.000684765 0.878718031 0.000416438 rc_AA469954_at 392 AA469954 0.239197445 0.004848961 0.288136551 0.000228067 0.913292289 0.000330413 rc_AA476594_i_at 393 AA476594 Arg/Abl-interacting 0.358342961 0.881892103 0.000846963 0.534258655 5.41111E-05 0.003508506 protein ArgBP2 rc_AA477119_at 395 AA477119 0.155425839 0.46185093 0.00021398 0.058896186 0.030447512 0.000152407 rc_AA477833_at 397 AA477833 translocase of inner 0.019542745 0.5471713 3.40147E-05 0.011694366 0.085999006 5.64814E-05 milochondrial membrane 44 (yeast) homolog rc_AA478615_s_at 398 AA478615 H1 histone family, 0.640957846 0.0022057 0.208838599 0.000871626 0.453348417 6.70146E-05 member X rc_AA478996_at 401 AA478996 0.680984202 0.000380025 0.977809564 0.000172484 0.677109345 0.000696316 rc_AA481057_f_at 404 AA481057 0.029606002 0.060557911 0.05307758 0.000302603 0.819130316 0.000643675 rc_aa482107_s_at 406 AA482107 0.412141577 0.217724563 0.000197553 0.061952573 1.63874E-05 0.055779976 rc_AA482559_at 407 AA482559 RPA-binding trans- 0.010341566 0.960676267 3.22844E-05 0.02919031 0.130837801 0.000454944 activator rc_AA485243_at 408 AA485243 leptin receptor 3.17405E-05 0.744743793 0.400224468 0.00016024 0.001638049 0.311163055 rc_AA488658_at 413 AA488658 hypothetical protein 0.000418682 0.365249562 0.186392502 0.000141589 0.036308821 0.048918937 rc_AA488849_at 414 AA488849 nucleotide binding 0.17603882 0.323192094 0.000687853 0.037989302 0.052798072 0.000161003 protein 2 (E.coli MinD like) rc_AA489637_at 415 AA489637 0.003960452 0.871859148 0.000107388 0.010699848 0.346672042 0.000730896 rc_AA490120_at 416 AA490120 0.082001486 0.454413511 0.000859271 0.030324764 0.130537834 0.000479561 rc_AA490520_at 418 AA490520 0.00063489 0.471991068 0.445872157 0.000410063 0.011810787 0.185068096 rc_AA490999_at 420 AA490999 0.001846648 0.670951196 0.000150658 0.002708195 0.521238606 0.000368557 rc_AA504255_at 423 AA504255 ataxia telangiectasia and 0.007747725 1.58087E-05 0.446946913 0.053347131 0.001163384 1.74835E-06 Rad3 related rc_AA505022_at 425 AA505022 0.250524892 0.000259519 0.084574205 7.98938E-06 0.584980634 7.63588E-07 rc_AA599376_at 435 AA599376 0.015748126 0.140670046 0.009272938 0.000615583 0.859099543 0.000343134 rc_AA599443_f_at 436 AA599443 hypothetical protein 0.379179145 0.00382066 0.40828628 0.000446702 0.960279666 0.000525999 FLJ10595 rc_AA609657_at 446 AA609657 7.04465E-05 0.091053447 0.00093271 0.092251403 0.5283101 0.25823308 rc_AA609848_at 447 AA609848 0.042723584 0.092999102 0.036171711 0.000967007 0.948118344 0.000787862 rc_AA609869_at 448 AA609869 hypothetical protein 4.47677E-05 0.00053907 2.12675E-07 0.943295205 0.293840522 0.321292026 FLJ13222 rc_AA610070_at 450 AA610070 calcium/calmodulin- 0.000126016 0.058243496 0.558814317 0.170494931 2.76548E-05 0.021111632 dependent serine protein kinase (MAGUK family) rc_AA620806_at 453 AA620806 ASB-3 protein 4.7861E-06 0.710135071 0.298838834 0.000563366 0.000797621 0.611912234 rc_AA621325_at 455 AA621325 HNK-1 sulfotransferase 0.000848661 0.346193012 0.004864951 0.000232221 0.621405553 0.001162331 rc_C14898_at 467 C14898 0.000226586 0.885711705 6.82551E-05 0.003389818 0.77964221 0.001496457 rc_C20547_at 469 C20547 0.068260402 0.000952953 0.812550962 2.71206E-06 0.132387942 0.000746928 rc_C20658_at 470 C20658 cisplatin resistance- 0.000322792 0.311886375 0.000285103 7.37384E-05 0.975640568 6.58868E-05 associated overexpressed protein rc_D11789_f_at 473 D11789 0.21798848 0.000243771 0.79113972 0.012426673 0.155631425 0.000180292 rc_D11961_at 475 D11961 hypothetical protein 0.066999427 0.031322113 0.050959636 0.000327468 0.909256528 0.000222056 FLJ21343 rc_D20085_at 479 D20085 0.533566658 0.000441315 0.321182892 0.004260671 0.125585439 2.65015E-05 rc_D52692_s_at 497 D52692 Ca2+-dependent 1.02115E-06 0.807110908 1.27404E-05 0.000127062 0.619779281 0.000681487 activator protein for secretion rc_D60272_i_at 499 D60272 0.000665091 0.000166097 0.000151004 0.431868883 0.714339713 0.641956827 rc_D80298_f_at 507 D80298 0.045427886 0.000323207 0.958861584 0.073418502 0.064448036 0.000644976 rc_D80738_f_at 509 D80738 0.190797369 0.00173762 0.245104642 4.17807E-05 0.889912758 7.00818E-05 rc_F01684_at 519 F01684 0.420181016 0.000494834 0.488322276 5.87948E-05 0.914533384 8.72831E-05 rc_F02739_at 525 F02739 5.54856E-05 0.053527575 0.000291424 0.133799091 0.698411971 0.246269511 rc_F04019_at 529 F04019 0.000166861 0.000950517 0.555841593 0.965823573 0.00259065 0.007252422 rc_F10193_at 539 F10193 chromosome 21 open 1.30777E-05 0.948962688 0.020624022 0.000363518 0.05248761 0.062247376 reading frame 39 rc_F10323_f_at 540 F10323 retinoblastoma-like 2 0.000650946 0.502771636 0.015425251 0.000500148 0.348990394 0.007831047 (p130) rc_F10980_at 541 F10980 8.9375E-05 0.653407439 0.012465868 0.000223205 0.178217348 0.012058063 rc_H01068_at 543 H01068 0.86517363 0.000569676 0.466764828 0.001528575 0.394499429 9.00281E-05 rc_H09077_at 551 H09077 3.06359E-05 1.2292E-05 0.021919052 0.46401342 0.07497746 0.021793621 rc_H11463_at 552 H11463 inhibitor of growth family, 0.00061851 0.000440258 0.000113152 0.597222623 0.678354487 0.869200328 member 3 rc_H14810_s_at 553 H14810 popeye protein 3 1.36532E-05 0.832182578 0.004057496 0.000637115 0.161519166 0.028710637 rc_H18099_at 560 H18099 0.247088588 0.003400663 0.301565366 0.000158641 0.90607919 0.000239103 rc_H23407_s_at 565 H23407 MAD1 (mitotic arrest 0.000753122 0.112093793 2.71462E-05 0.201584279 0.432877141 0.049424886 deficient, yeast, homolog)-like 1 rc_H23520_at 566 H23520 0.611355729 0.000871266 0.849483973 0.000293132 0.507906287 0.002361124 rc_H38418_at 570 H38418 0.185134143 0.065592241 0.008782561 0.50515013 0.000181804 7.8388E-05 rc_H38995_f_at 571 H38995 KIAAO471 gene product 0.009631356 0.97045862 5.86902E-05 0.028554385 0.175136692 0.000728104 rc_H45265_at 574 H45265 ATP-binding cassette, 0.000152193 4.19671E-07 0.003258301 0.08727525 0.422648726 0.015812939 sub-family A (ABC1), member 7 rc_H48263_at 575 H48263 0.185258234 0.007096561 0.191295818 0.00022522 0.986389253 0.000238835 rc_H48475_at 576 H48475 ribosomal protein L37a 0.227463546 0.00062116 0.579381783 1.76941E-05 0.535824365 0.000177441 rc_H58781_at 582 H58781 0.042650671 0.000369904 0.497627082 0.082860732 0.010272658 6.73936E-05 rc_H59141_at 584 H59141 hypothetical protein 0.001248184 4.64747E-07 0.066732688 0.031003204 0.185961631 0.000909745 rc_H63994_at 588 H63994 0.042052556 0.003078049 0.051932289 5.75286E-06 0.93248223 8.15902E-06 rc_H64411_at 589 H64411 KIAA0618 gene product 0.01802462 0.070417348 0.012928934 0.000210449 0.908905166 0.000140956 rc_H77531_s_at 593 H77531 HIR (histone cell cycle 0.000791123 0.49434307 0.184056577 0.00056294 0.054421223 0.078090378 regulation defective, S. cerevisiae) homolog A rc_H97868_at 608 H97868 0.322057918 0.489184724 0.000285548 0.136645099 0.012333089 0.000230315 rc_H97889_at 609 H97889 0.158642014 0.00916284 0.299358664 0.000236375 0.724266848 0.00075937 rc_H98676_at 610 H98676 0.127756769 0.002896791 0.262913685 3.64577E-05 0.701889069 0.000148754 rc_N20967_at 717 N20967 9.92879E-05 0.817666422 3.00688E-05 0.000539948 0.790070901 0.000221099 rc_N22115_s_at 720 N22115 KIAA0447 gene product 5.18274E-07 0.014513808 3.98659E-05 0.067547386 0.387363889 0.284673955 rc_N22297_f_at 721 N22297 0.054494667 0.052949003 0.08027668 0.000541487 0.869037035 0.000917296 rc_N32521_at 735 N32521 hypothetical protein 0.547891484 0.041933612 0.000238523 0.014113039 0.003549591 5.39907E-07 FLJ11085 rc_N34517_s_at 738 N34517 integrin, alpha 7 0.005879801 0.196182153 0.004385481 0.00040993 0.928485921 0.000303466 rc_N38882_at 741 N38882 0.014629787 0.005666897 0.251351421 0.530957263 0.000663242 0.000303436 rc_N51579_at 748 N51579 transporter-like protein 0.44766874 6.17952E-05 0.962144968 0.001295779 0.499475206 0.00139415 rc_N54053_at 752 N54053 secreted phosphoprotein 0.116492665 0.015273471 0.039361645 0.00027615 0.641546757 5.23218E-05 2, 24 kD rc_N54845_at 753 N54845 0.000443555 0.073889565 0.000793416 0.227981278 0.881125278 0.282635582 rc_N55085_at 754 N55085 0.220208071 0.876075911 0.000843717 0.384166413 1.49242E-05 0.003419797 rc_N59862_at 760 N59862 0.462122243 0.001300248 0.276791676 0.000214232 0.741521525 6.58223E-05 rc_N66001_at 765 N66001 mouse double minute 4, 0.269409972 0.001627722 0.449591713 7.93964E-05 0.741058833 0.000255792 human homolog of; p53- binding protein rc_N66053_f_at 766 N66053 butyrophilin, subfamily 3, 0.000767668 0.638609685 0.000120387 0.018876455 0.648066184 0.005990603 member A1 rc_N67108_at 769 N67108 2.22447E-05 0.94547199 0.335823565 0.000534028 0.00186846 0.462281008 rc_N67324_at 770 N67324 0.061297249 0.015332682 0.029486337 0.000101757 0.771895611 3.46367E-05 rc_N67899_at 774 N67899 8.19817E-05 0.845939057 0.027139019 0.000532728 0.100944503 0.04285656 rc_N80693_at 787 N80693 0.798568519 0.000819546 0.654401168 0.002677747 0.504907369 0.000334108 rc_N89827_at 788 N89827 RALBP1 associated Eps 0.129696038 0.000403735 8.58239E-05 0.032513633 0.022112053 0.895818166 domain containing 2 rc_N93495_at 795 N93495 uncharacterized 0.082365924 0.047090947 0.00063645 0.000799522 0.111310122 2.03892E-06 hematopoietic stem/progenitor cells protein MDS033 rc_R00440_at 802 R00440 ancient conserved 0.538637852 6.90248E-05 0.927092838 0.000926675 0.619532275 0.000178704 domain protein 4 rc_R17000_s_at 812 R17000 NADH dehydrogenase 0.000151792 0.075089669 0.000101925 0.149353698 0.926045731 0.12770179 (ubiquinone) Fe-S protein 8 (23 kD) (NADH- coenzyme Q reductase) rc_R25116_at 813 R25116 0.0420832 0.03125809 0.026701279 0.000169518 0.862052816 9.11635E-05 rc_R40030_at 827 R40030 hypothetical protein 0.567472456 0.000280009 0.804462147 0.002571098 0.436977215 0.000218515 FLJ20047 rc_R41798_s_at 829 R41798 KIAA1374 protein 0.000373432 0.706910506 0.012448736 0.000894251 0.315054178 0.014659398 rc_R42336_s_at 831 R42336 0.70873782 2.16988E-05 0.77916386 0.000163747 0.929588049 0.000119701 rc_R42525_at 833 R42525 0.050001405 0.071849508 0.013930003 0.000778775 0.635857474 0.000159677 rc_R56216_at 845 R56216 0.000821825 0.352494161 0.151440792 0.0002362 0.069860079 0.036903476 rc_R66690_at 851 R66690 0.548034357 0.001498849 0.392082801 0.000384981 0.808745096 0.000168251 rc_R702125_s_at 853 R70212 CD79A antigen 0.001627385 0.92358255 1.96242E-05 0.011419498 0.28878538 0.000540241 (immunoglobulin- associated alpha) rc_R82942_s_at 856 R82942 4.27278E-06 0.038346252 9.40527E-05 0.06641734 0.511382181 0.207797821 rc_R84968_at 858 R84968 0.029165843 9.17654E-05 0.74623486 0.052010697 0.078018241 0.0004854 rc_R89291_at 861 R89291 0.000287625 0.129809655 0.120359785 7.72734E-06 0.049234398 0.005999323 rc_R92737_at 864 R92737 aquaporin 3 0.045317535 0.54600908 0.000762777 0.024731156 0.195577177 0.000722979 rc_T15530_at 879 T15530 0.039751248 0.193908111 0.000219396 0.003085344 0.119916961 1.53896E-05 rc_T16556_at 882 T16556 0.547027876 0.000735355 0.131501406 0.006096912 0.045271057 6.8433E-06 rc_T49291_s_at 895 T49291 lymphocyte-specific 0.023580272 0.159004442 0.000765019 0.00120856 0.296144015 3.27932E-05 protein 1 rc_T50387_at 897 T50387 0.685476265 0.000770227 0.324729565 0.003799426 0.187347142 5.10594E-05 rc_T53404_at 898 T53404 hypothetical protein from 0.47780256 0.003673041 0.259379562 0.000720609 0.69168737 0.000191916 clone 643 rc_T54613_at 900 T54613 5.52684E-05 0.022747185 0.000284729 0.24335011 0.701984774 0.40594297 rc_T54617_at 901 T54617 0.857947447 4.07249E-05 0.397904433 0.000146584 0.527265593 0.001199664 rc_T65802_at 908 T65802 0.012663512 0.532196596 0.000313482 0.007483397 0.291974796 0.000319721 rc_T79868_f_at 915 T79868 hypothetical protein 0.071499128 0.033264086 0.074047238 0.000392669 0.987909984 0.000412941 384D8_6 rc_T82292_s_at 916 T82292 protease, serine, 11 (IGF 0.000399556 0.678142361 0.051597503 0.000824339 0.130506724 0.043561586 binding) rc_T86121_at 918 T86121 0.013631945 0.898945913 2.7658E-06 0.029665506 0.035142628 5.76483E-05 rc_T87533_at 920 T87533 0.989160192 0.000472522 0.640089183 0.000751611 0.648053004 0.002981136 rc_T90038_f_at 924 T90038 butyrophilin, Subfamily 3, 4.93914E-06 0.243601757 8.38948E-05 0.007362582 0.547300658 0.031384668 member A2, butyrophilin, subfamily 3, member A3 rc_T99373_at 934 T99373 0.026021837 3.07604E-06 0.711043501 0.008523742 0.078371167 2.98773E-05 rc_W37384_i_at 1001 W37384 non-metastatic cells 5, 0.000625839 0.217732697 0.000147234 0.096608548 0.7216482 0.048383963 protein expressed in (nucleoside-diphosphate kinase) rc_W42483_at 1003 W42483 hypothetical protein 2.97466E-05 0.676684762 0.031770051 0.000106724 0.05435082 0.028721568 similar to mouse Dnajl1 rc_W44558_s_at 1005 W44558 adaptor-related protein 0.079864992 0.042988764 0.034848175 0.000669599 0.73367308 0.000215475 Complex 1, sigma 1 subunit rc_W60649_at 1019 W60649 0.023339325 0.129224665 0.006757142 0.000824018 0.675851904 0.000206179 rc_W80509_s_at 1032 W80509 death associated 0.000271744 0.148661601 0.000426903 0.10048575 0.910884693 0.122505852 transcription factor 1 rc_W86660_at 1034 W86660 0.150249394 6.18841E-06 0.557722374 0.001658036 0.418699422 0.000115844 rc_W93396_at 1038 W93396 0.000180228 0.540603359 0.319667744 0.00021213 0.009081674 0.156804025 rc_Z38551_s_at 1107 Z38551 hypothetical protein 0.007617909 0.125060522 0.00394587 0.000220695 0.839190935 0.000107925 FLJ10210 rc_Z39874_at 1110 Z39874 0.018342738 0.000251552 0.969844211 0.120049181 0.022998914 0.000387407 rc_Z40012_f_at 1113 Z40012 NCK-associated protein 0.038639336 0.043854062 0.05138364 0.000255085 0.909554475 0.000374451 rc_Z40332_at 1115 Z40332 vesicle docking protein 0.028012659 0.10943539 0.012529791 0.000762549 0.7761268 0.000299824 p115 rc_Z41763_at 1120 Z41763 6.03127E-05 0.82776366 0.002670862 0.00038983 0.338788944 0.006770727 S75463_at 871 S75463 Tu translation elongation 0.000271911 0.000533911 0.00172916 0.765671272 0.63019533 0.471338415 factor, mitochondrial S77154_s_at 872 S77154 nuclear receptor 0.720602576 0.932154297 5.84424E-05 0.829150677 0.000513773 0.001105408 subfamily 4, group A, member 2 T40327_s_at 891 T40327 electron-transferring- 7.27596E-06 0.215221988 0.819260055 0.011040692 7.74754E-06 0.167330005 flavoprotein dehydrogenase T89243_s_at 922 T89243 KIAA1243 protein 0.00081408 0.517949226 0.114764867 0.000657245 0.092965856 0.053186849 U00672_at 935 U00672 interleukin 10 receptor, 0.000287943 0.609290849 1.66617E-06 0.011540026 0.269359727 0.000474683 alpha U03272_at 937 U03272 fibrillin 2 (congenital 0.000310928 0.332521737 0.209649826 8.44451E-05 0.025692948 0.04828388 contractural arachnodactyly) U04811_at 939 U04811 trophinin 1.5625E-05 0.755433375 0.054905474 0.000984445 0.022792101 0.194301082 U04811_at 939 U04811 trophinin 2.20509E-06 0.327834193 0.000136465 0.002712738 0.383208442 0.025499623 U09366_at 943 U09366 zinc finger protein 133 0.000213171 0.5068558 0.610828511 0.000200267 0.002444941 0.288631384 (clone pHZ-13) U11861_at 945 U11861 maternal G10 transcript 0.000482828 0.00167301 9.90184E-05 0.90794872 0.702310162 0.826191525 U12775_at 946 U12775 agouti (mouse)-signaling 0.000271316 0.000844452 0.000473875 0.859392382 0.889729458 0.765131751 protein U13220_at 947 U13220 forkhead box F2 0.000592743 0.851887641 3.88357E-05 0.007392289 0.519237 0.001178975 U13991_at 948 U13991 TATA box binding 1.45014E-06 0.006140037 1.01255E-06 0.168790439 0.946149483 0.151190281 protein (TBP)-associated factor, RNA polymerase II, H, 30 kD U15932_at 949 U15932 dual specificity 0.877505283 0.806495835 1.85723E-05 0.914714787 2.57739E-05 0.000146058 phosphatase 5 U23852_s_at 954 U23852 lymphocyte-specific 0.015926444 0.891018698 9.08522E-05 0.032567274 0.153847965 0.000703723 protein tyrosine kinase U25265_at 957 U25265 mitogen-activated protein 8.86395E-06 0.005417963 5.93432E-05 0.305372601 0.684875389 0.503461673 kinase kinase 5 U26174_at 959 U26174 granzyme K (serine 3.92686E-05 0.206902143 0.000598254 0.027205202 0.519267093 0.10031708 protease, granzyme 3, tryptase II) U32674_s_at 962 U32674 G protein-coupled 0.003147245 0.1818672 0.076391484 0.000184255 7.37649E-06 0.847933992 receptor 9 U40372_at 963 U40372 phosphodiesterase 1C, 0.284766484 1.17113E-05 0.46702597 0.000897191 0.745348724 0.000311221 calmodulin-dependent (70 kD) U43527_at 966 U43527 KiSS-1 metastasis- 0.068750933 0.878566298 0.000141006 0.096679594 0.059509384 0.000920023 suppressor U46006_s_at 968 U46006 cysteine and glycine-rich 0.000581958 0.677096089 0.000421368 0.013813896 0.93464395 0.011277242 protein 2 U52112_at 969 U52112 L1 cell adhesion 0.012256648 0.603209864 0.000361314 0.0009782964 0.313616052 0.000525936 molecule (hydrocephalus, stenosis of aqueduct of Sylvius 1, MASA (mental retardation, aphasia, Shuffling gait and adducted thumbs) syndrome, spastic paraplegia 1) U55209_at 973 U55209 myosin VIIA (Usher 0.026307797 0.000534284 5.50778E-05 0.139252083 0.085728294 0.977237559 syndrome lB (autosomal recessive, severe)) U57623_s_at 975 U57623 fatty acid binding protein 0.000249597 0.006076702 2.31411E-07 0.680669423 0.152138423 0.095412354 3, muscle and heart (mammary-derived growth inhibitor) U58522_at 976 U58522 huntingtin interacting 0.950874668 0.000404266 0.026015373 0.000816174 0.04004298 0.12201215 protein 2 U66075_at 980 U66075 GATA-binding protein 6 0.000177786 0.094949773 5.41966E-05 0.129840147 0.784613111 0.079354568 U66615_at 981 U66615 SWI/SNF related, matrix 0.00427057 0.860602352 0.000125812 0.01088834 0.353965999 0.000781605 associated, actin dependent regulator of chromatin, subfamily c, member 1 U89922_s_at 987 U89922 lymphotoxin beta (TNF 0.081431989 0.705262065 1.14225E-05 0.069803458 0.012069263 5.95219E-05 superfamily, member 3) W52493_at 1013 W52493 4.17744E-05 0.407939223 0.47764998 2.61848E-05 0.001311163 0.165780725 X06318_at 1048 X06318 protein kinase C, beta 1 4.53981E-05 0.309598889 0.000193355 0.01564851 0.739435449 0.033561473 X07315_at 1053 X07315 nuclear transport factor 2 0.00096734 0.024484461 0.000991289 0.558914618 0.994799819 0.56276584 (placental protein 15) X14008_rna1_f_at 1056 X14008 lysozyme (renal 0.047298803 0.921767172 1.2563E-05 0.081015792 0.023720356 0.000192698 amyloidosis) X14046_at 1057 X14046 CD37 antigen 0.032116442 0.896768704 6.54708E-06 0.097237805 0.024859085 0.000287679 X14830_at 1058 X14830 cholinergic receptor, 0.936178672 0.000286907 0.137976127 0.000630986 0.183095639 0.024428637 nicotinic, beta polypeptide 1 (muscle) X16316_at 1059 X16316 vav 1 oncogene 0.005646314 0.4794965 0.000157845 0.002861938 0.337620027 0.00013174 X54870_at 1065 X54870 DNA segment on 0.000450913 0.241248516 0.00029577 0.07293822 0.916408 0.059393045 chromosome 12 (unique) 2489 expressed sequence X58529_at 1070 X58529 immunoglobulin heavy 0.026942297 0.975028968 5.32141E-08 0.070184957 0.002196974 6.90925E-06 constant mu X60673_s_at 1072 X60673 adenylate kinase 3 0.014055428 1.64563E-05 0.000854329 0.036097108 0.40449053 0.17235001 X63741_s_at 1074 X63741 early growth response 3 0.050166995 0.302932401 1.63652E-08 0.522269647 0.000467351 0.000208487 X66358_at 1079 X66358 cyclin-dependent kinase- 3.6744E-05 0.079324094 3.35901E-05 0.080441339 0.984409054 0.077518373 like 1 (CDC2-related kinase) X66839_at 1080 X66839 carbonic anhydrase IX 3.93574E-06 0.662915937 0.008885816 0.000624117 0.057988735 0.078713562 X68277_at 1082 X68277 dual specificity 0.003463894 0.023542489 5.00933E-13 0.79747022 4.48312E-05 0.000125081 phosphatase 1 X72882_at 1084 X72882 0.000586574 1.73881E-05 0.061863645 0.20511364 0.136254698 0.010057929 X75962_at 1085 X75962 hypothetical protein 1.07753E-05 0.259082214 0.000322398 2.07333E-06 0.445393473 4.56511E-05 FLJ10747,tumor necrosis factor receptor superfamily, member 4 X83705_s_at 1089 X83705 platelet-derived growth 0.000211219 0.000641028 0.003169595 0.843987656 0.474177301 0.409652768 factor beta polypeptide (simian sarcoma viral (v- sis) oncogene homolog) X96584_at 1096 X96584 nephroblastoma 0.000449835 0.36091834 0.013539811 0.00014621 0.323949108 0.003364493 overexpressed gene X99142_at 1097 X99142 keratin, hair, basic, 6 0.104620098 0.022019682 0.075077447 0.00038452 0.881497721 0.000232112 (monilethrix) Y07595_at 1099 Y07595 general transcription 0.000268402 0.028695565 5.26844E-05 0.352269642 0.704788647 0.206775434 factor IIH, polypeptide 4 (52 kD subunit) Y09022_at 1102 Y09022 Not56 (D. melanogaster)- 0.000142024 0.084289616 0.000108418 0.131801466 0.949831739 0.118236485 like protein Z35093_at 1105 Z35093 surfeit 1 0.000740458 0.015177247 0.000173743 0.635076989 0.718277145 0.428942461

[0147]

0 SEQUENCE LISTING The patent application contains a lengthy “Sequence Listing” section. A copy of the “Sequence Listing” is available in electronic form from the USPTO web site (http://seqdata.uspto.gov/sequence.html?DocID=20030134280). An electronic copy of the “Sequence Listing” will also be available from the USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3). 

We claim:
 1. A method of screening for or identifying an agent that modulates the onset or progression of benign prostatic hyperplasia (BPH), comprising: (a) preparing a first gene expression profile of BPH cells or BPH-like cell population; (b) exposing the cells to the agent (c) preparing second gene expression profile of the agent exposed cells; and (d) comparing the first and second gene expression profiles.
 2. A method of claim 1, wherein the gene expression profile comprises the expression levels for one or more genes that are differentially regulated in BPH cells compared to normal prostate cells.
 3. A method of claim 1, wherein the agent modulates the expression levels for one or more genes in the BPH cells to levels close or similar to the expression level found in normal prostate cells.
 4. A method of claim 1, wherein the gene expression profile comprises the expression levels in BPH cells for one or more genes in Tables 1-6.
 5. A method of claim 1, wherein the gene expression profile comprises the expression levels in BPH cells for one or more genes in Table
 5. 6. A method of any one of claims 1-5, wherein the BPH cell is selected from the group consisting of prostate cells from a BPH patient, a cell line in Table 7 and a derivative thereof.
 7. A method of any one of claims 2-5, wherein the expression levels are for two or more genes.
 8. A method of diagnosing the onset or progression of benign prostatic hyperplasia (BPH) in a subject comprising: (a) detecting the expression levels of one or more genes in prostate cells from the subject that are differentially regulated compared to normal prostate cells.
 9. A method of claim 8, wherein the expression levels are for one or more genes in Tables 1-6.
 10. A method of claim 8, wherein the expression levels are for two or more genes in Tables 1-6.
 11. A method of claim 8, wherein the expression levels are for one or more genes in Table
 5. 12. A method of claim 8, wherein the expression levels are for two or more genes in Table
 5. 13. A method of differentiating benign prostatic hyperplasia (BPH) from prostate cancer in a subject comprising: (a) detecting the expression levels of one or more genes in prostate cells from the subject that are indicative of BPH rather than prostate cancer.
 14. A method of claim 13, wherein the expression levels are for one or more genes in Tables 1-6.
 15. A method of claim 13, wherein the expression levels are for two or more genes in Tables 1-6.
 16. A method of claim 13, wherein the expression levels are for one or more genes in Table
 5. 17. A method of claim 13, wherein the expression levels are for two or more genes in Table
 5. 18. A set of oligonucleotide probes, wherein each of the probes specifically hybridizes to a gene in Tables 1-6.
 19. A set of oligonucleotide probes, wherein each of the probes specifically hybridizes to a gene in Table
 5. 20. A set of oligonucleotide probes of claim 18, wherein the set specifically hybridizes to nearly all the genes in Tables 1-6.
 21. A set of oligonucleotide probes of claim 18, wherein the set specifically hybridizes to nearly all the genes in Table
 5. 22. A set of oligonucleotide probes of any one of claims 18-21, wherein the probes are attached to a solid support.
 23. A set of oligonucleotide probes of claim 22, wherein the solid support is selected from the group consisting of a membrane, a glass support and a silicon support.
 24. A solid support onto which two or more oligonucleotide probes have been attached, wherein each of the probes specifically hybridizes to a gene in Tables 1-6.
 25. A solid support of claim 24, wherein the probes specifically hybridize to nearly all of the genes in Tables 1-6.
 26. A solid support onto which two or more oligonucleotide probes have been attached, wherein the probes specifically hybridize to a gene in Table
 5. 27. A solid support of claim 26, wherein the probes specifically hybridize to nearly all of the genes in Table
 5. 28. A solid support of any one of claims 24-27, wherein the solid support is an array comprising at least 10 different oligonucleotides in discrete locations per square centimeter.
 29. A solid support of claim 28, wherein the array comprises at least 100 different oligonucleotides in discrete locations per square centimeter.
 30. A solid support of claim 28, wherein the array comprises at least 1000 different oligonucleotides in discrete locations per square centimeter.
 31. A solid support of claim 28, wherein the array comprises at least 10,000 different oligonucleotides in discrete locations per square centimeter.
 32. A computer system comprising: (a) a database containing information identifying the expression level in benign prostatic hyperplasia (BPH) tissue or cells of a set of genes comprising at least two genes in Tables 1-6; and (b) a user interface to view the information.
 33. A computer system of claim 32, wherein the set of genes comprises at least two genes in Table
 5. 34. A computer system of claim 32, wherein the database further comprises sequence information for the genes.
 35. A computer system of claim 32, wherein the database further comprises information identifying the expression level for the set of genes in normal prostate tissue or cells.
 36. A computer system of claim 32, wherein the database further comprises information identifying the expression level of the set of genes in prostate cancer tissue or cells.
 37. A computer system of claim 32, further comprising records including descriptive information from an external database, which information correlates said genes to records in the external database.
 38. A computer system of claim 37, wherein the external database is GenBank.
 39. A method of using a computer system of claim 32 to present information identifying the expression levels in a tissue or cells of at least one gene in Tables 1-6, comprising the step of: (a) comparing the expression level of at least one gene in Tables 1-6 in the tissue or cells to the level of expression of the gene in the database.
 40. A method of claim 39, wherein the expression levels of at least two genes are compared.
 41. A method of claim 39, wherein the expression levels of at least five genes are compared.
 42. A method of claim 39, wherein the expression levels of at least ten genes are compared.
 43. A method of claim 39, further comprising the step of displaying the expression levels of at lest one gene in the tissue or cell sample compared to the expression level in BPH.
 44. A method of monitoring the treatment of a patient with benign prostatic hyperplasia (BPH), comprising: (a) administering a pharmaceutical composition to the patient; (b) preparing a gene expression profile from a cell or tissue sample from the patient; and (c) comparing the patient gene expression profile to a gene expression profile from a normal prostate cells, or a BPH tissue or cell sample without treatment.
 45. A method of claim 44, wherein the gene expression profile comprises the expression levels for one or more genes in Tables 1-6.
 46. A method of claim 44, wherein the gene expression profile comprises the expression levels for one or more genes in Table
 5. 47. A method of claim 45 or 46, wherein the expression levels are for two or more genes.
 48. A method of any one of claims 1, 8, 12, 38 or 43, wherein the gene expression profile or gene expression level is detected by branched DNA (bDNA) method.
 49. A computer readable storage medium storing a computer program for implementing an algorithm executing method of analyzing gene expression results; said method comprising: (a) converting the mean expression value for each gene to 0; and (b) converting the high and low expression values to 1 and −1, respectively.
 50. The medium of claim 49, wherein the method further comprises the step of: (c) clustering the converted expression values to identify sets of genes with similar expression pattern. 